Molecular
mechanisms of the effect of protein-peptide hormones on the target cells.
Molecular mechanisms of the
effect of catecholamines and another biological amines on target cells
The survival of multicellular organisms
depends on their ability to adapt to a constantly changing environment.
Intercellular communication mechanisms are necessary requirements for this
adaptation. The nervous system and the endocrine system provide this
intercellular, organism- wide communication. The nervous system was originally
viewed as providing a fixed communication system, whereas the endocrine system
supplied hormones, which are mobile messages. In fact, there is a remarkable
convergence of these regulatory systems. For example, neural regulation of the
endocrine system is important in the production and secretion of some hormones;
many neurotransmitters resemble hormones in their synthesis, transport, and
mechanism of action; and many hormones are synthesized in the nervous system.
Endocrine vs. Nervous System
Nervous
System |
Endocrine
System |
Neurons release neurotransmitters |
Endocrine cells release hormones |
A neurotransmitter acts on specific
cell right next to it. |
Hormones travel to another nearby cell
or act on cell in another part of the body. |
Neurotransmitters have their effects
within milliseconds. |
Hormones take minutes or days to have
their effects. |
The effects of neurotransmitters are
short-lived. |
The effects of hormones can last hours,
days, or years. |
Performs short term crisis management |
Regulates long term ongoing metabolic
function |
Neurotransmitter acts on specific
cell right next to it. |
Hormone can travel to another nearby
cell or it can act on another part of the body. |
The word “hormone” is
derived from a Greek term that means to arouse to activity. As classically
defined, a hormone is a substance that is synthesized in one organ and
transported by the circulatory system to act on another tissue. They are secreted in
response to changes in the environment inside or outside the body. These are
released into the extracellular fluid, where they are diffused into the blood
stream. The latter carries them from the site of production to the site of action.
They act on specific organs called
target organs. The blood contains all the hormones but the cells of a
target organ can pick up the specific required hormone only and ignore all
others. It has been found that the target cell has on its surface or in its
cytoplasm a specific protein molecule, called a receptor, which can recognise
and pick out the specific hormone capable of action in that cell. The hormone
delivers its message to the target cell by changing the shape of the receptor
cell and binds to it. The receptors new shape sets up certain changes in the
cell such as alteration in permeability, enzyme activity or gene transcription.
http://www.youtube.com/watch?v=kIPYVV4aThM&feature=related
Hormones may stimulate or inhibit
specific biological processes in the target organs to modify their activities
thus acting as regulators. There is considerable co-ordination between nerves
and hormones. Nerves regulate synthesis and release of some hormones. Some
times hormones may also influence nerve activities. Thus, hormonal
co-ordination plays an important role in regulating body functions.
Calcitonin secreted by thyroid
gland regulates the concentration of calcium and phosphorus in the blood. When
the concentration of calcium rises in the blood, the secretion of calcitonin is
seen which lowers the concentration of calcium and phosphorus in the plasma by
decreasing the release for the bones.
Maintenance
of internal chemical environment of the body to a constant is called
homeostasis. Hormones play a major role in maintaining homeostasis by their
intergrated action and feed back controls.
Feedback control is mostlly negative,
rarely positive. In a negative feedback control, synthesis of a hormone slows
or halts when its level in the blood rises above normal. Some of examples of
feedback control is given below.
Rise of
testosterone level in the blood above normal inhibits ICSH secretion by the
anterior pituitary lobe. This negative feedback checks oversecretion of
testosterone
Hypothalamus in response to some
external stimulus, produces a thyrotrophin-releasing hormone for the secretion
of thyrotrophic hormone. The thyrotrophin-releasing hormone (TRH) stimulates
the anterior pituitary lobe to secrete thyrotrophic hormone. The latter in turn
stimulates the thyroid gland to produce thyroxine. If thyroxine is in excess,
it exerts an influence on the hypothalamus and anterior pituitary lobe, which
then secrete less releasing hormone and thyroid-stimulating hormone (TSH)
respectively. A rise in the TSH level in the blood may also exert negative feed
back effect on the hypothalmus and retard the secretion of TRH. This restores
the normal blood-thyroxine level.
Functions of
hormones.
Hormones regulate the following processes:
Growth and
differentiation of cells, tissues, and organs These
processes include cell proliferation, embryonic development, and sexual
differentiation— i. e., processes that require a prolonged time period and
involve proteins de novo synthesis. For this reason, mainly steroid hormones
which function via transcription regulation are active in this field
Metabolic pathways
Metabolic regulation requires rapidly acting
mechanisms. Many of the hormones involved therefore regulate interconversion
of enzymes. Themain processes subject to hormonal regulation are the uptake
and degradation of storage substances (glycogen, fat), metabolic pathways for
biosynthesis and degradation of central metabolites (glucose, fatty acids,
etc.), and the supply of metabolic energy.
Digestive
processes Digestive
processes are usually regulated by locally acting peptides (paracrine), but mediators,
biogenic amines, and neuropeptides are also involved.
Maintenance
of ion concentrations (homeostasis) Concentrations
of Na+, K+, and Cl– in body fluids, and the physiological variables dependent
on these (e. g. blood pressure), are subject to strict regulation. The
principal site of action of the hormones involved is the kidneys, where
hormones increase or reduce the resorption of ions and recovery of water. The
concentrations of Ca2+ and phosphate, which form the mineral substance of bone
and teeth, are also precisely regulated. Many hormones influence the above
processes only indirectly by regulating the synthesis and release of other
hormones (hormonal hierarchy).
3.
Endocrine, paracrine, and autocrine
hormone effects.
http://www.youtube.com/watch?v=3LW7TSBcFjE&feature=related
Hormones transfer signals by migrating from heir
site of synthesis to their site of action. They are usually transported in the
blood. In this case, they are said to have an endocrine effect (example:
insulin). By contrast, tissue hormones, the target cells for
which are in the immediate vicinity of the glandular cells that produce them,
are said to have a paracrine effect (example: gastrointestinal tract
hormones). When signal substances also pass effects back to the cells that
synthesize them, they are said to have an autocrine effect (example: prostaglandins).
Autocrine effects are often found in tumor cells, which stimulate their own
proliferation in this way. Insulin,which is formed in the B cells of the
pancreas, has both endocrine and paracrine effects. As a hormone with endocrine
effects, it regulates glucose and fat metabolism. Via a paracrinemechanism, it
inhibits the synthesis and release of glucagon from the neighboring A
cells.
Endocrine glands
The endocrine system is made
up of glands that produce and secrete hormones, chemical substances produced in
the body that regulate the activity of cells or organs. These hormones regulate
the body's growth, metabolism (the physical and chemical processes of the
body), and sexual development and function. The hormones are released into the
bloodstream and may affect one or several organs throughout the body.
The major glands of the endocrine
system are the hypothalamus, pituitary, thyroid, parathyroids, adrenals, pineal
body, and the reproductive organs (ovaries and testes). The pancreas is also a
part of this system; it has a role in hormone production as well as in
digestion.
The endocrine system is
regulated by feedback in much the same way that a thermostat regulates the
temperature in a room. For the hormones that are regulated by the pituitary
gland, a signal is sent from the hypothalamus to the pituitary gland in the
form of a "releasing hormone," which stimulates the pituitary to
secrete a "stimulating hormone" into the circulation.
The
stimulating hormone then signals the target gland to secrete its hormone. As
the level of this hormone rises in the circulation, the hypothalamus and the
pituitary gland shut down secretion of the releasing hormone and the
stimulating hormone, which in turn slows the secretion by the target gland.
This system results in stable blood concentrations of the hormones that are
regulated by the pituitary gland.
Classification
of hormones.
The animal
organism contains more than 100 hormones and hormone-like substances, which can
be classified either according to their structure or according to their
function. In chemical terms, most hormones are:
Ø hormones of protein structure: all
hormones of anterior pituitary (except ACTH), insulin, parathyroid hormone;
Ø hormones of peptide structure: ACTH,
calcitonin, glucagon, hormones of posterior pituitary, factors of hypothalamus,
thymozin;
Ø
steroid
hormones: adrenal cortical steroids, sex hormones;
Ø
Ø hormones - derivatives of amino acid:
thyroid hormones, adrenal medulla hormones, epiphysis hormones;
Ø
Ø hormones derivatives of unsaturated
fatty acid: prostaglandins.
Pathways in biosynthesis of eicosanoids from arachidonic acid:
there are parallel paths from
v Lipotrophic
v
Hydrophilic
http://www.youtube.com/watch?v=kIPYVV4aThM&feature=related
http://www.youtube.com/watch?v=8fh2HmdxQjQ&feature=related
Mechanism of
action
A.
Mechanism of action of lipophilic
hormones
Lipophilic
signaling substances include the steroid hormones, calcitriol, the iodothyronines
(T3 and T4), and retinoic acid. These hormones mainly act in the nucleus
of the target cells, where they regulate gene transcription in
collaboration with their receptors and with the support of additional proteins
(known as coactivators and mediators). There are several effects of steroid
hormones that are notmediated by transcription control. These alternative
pathways for steroid effects have not yet been fully explained. In the blood,
there are a number of transport proteins for lipophilic hormones. Only the free
hormone is able to penetrate the membrane and enter the cell. The hormone
encounters its receptor in the nucleus (and sometimes also in the cytoplasm).
The receptors for lipophilic hormones are rare proteins. They occur in
small numbers (103–104 molecules per cell) and show marked specificity and
high affinity for the hormone (Kd = 10–8–10–10 M). After binding
to the hormone, the steroid receptors are able to bind as homodimers or
heterodimers to control elements in the promoters of specific genes,
from where they can influence the transcription of the affected genes—i. e.,
they act as transcription factors. The illustration shows the
particularly well-investigated mechanism of action for cortisol, which
is unusual to the extent that the hormone–receptor complex already arises in
the cytoplasm. The free receptor is present in the cytoplasm as a monomer in
complex with the chaperone hsp90. Binding of cortisol to the complex
leads to an allosteric conformational change in the receptor, which is
then released from the hsp90 and becomes capable of DNA binding as a result of dimerization.
In the nucleus, the hormone–receptor complex binds to nucleotide sequences
known as hormone response elements (HREs).
The second mechanism involves steroid hormones, which pass
through the plasma membrane and act in a two step process. Steroid hormones
bind, once inside the cell, to the nuclear membrane receptors, producing an
activated hormone-receptor complex. The activated hormone-receptor complex
binds to DNA and activates specific genes, increasing production of proteins.
|
|
These are short palindromic DNA segments that usually
promote transcription as enhancer elements. The illustration shows the HRE for
glucocorticoids (GRE; “n” stands for any nucleotide). Each hormone receptor
only recognizes its “own” HRE and therefore only influences the transcription
of genes containing that HRE. Recognition between the receptor and HRE is based
on interaction between the amino acid residues in the DNA-binding domain (B)
and the relevant bases in the HRE (emphasized in color in the structure
illustrated). As discussed on p. 244, the hormone receptor does not interact
directly with the RNA polymerase, but rather—along with other transcription
factors—with a coactivator/mediator complex that processes all of the signals
and passes them on to the polymerase. In this way, hormonal effects lead within
a period of minutes to hours to altered levels ofmRNAs for key proteins in
cellular processes (“cellular response”).
B.
Mechanism of action of hydrophilic
hormones
The
hormones are released in very small quantities, yet they can cause widespread
dresponses in cells or tissues all over the body. These responses in cells or
tissues all over the body. These responses can be quite specific and selective
in different cells. All vertebrate hormones belong to one of four chemical
groups. Some hormones, such hormone, such as adrenaline and thyroid hormone,
are small molecules derived from the amino acid tyrosine, others such as
vasopressin and oxytocin, are short peptides, still other hormones, like
insulin and glucagons, are longer polypeptide chains. Testosterone and estrogen
are steroid hormones. Catecholamines, peptide and protein hormones are not
lipid-soluble, and so, cannot enter their target cells through the bilipid
layer of plasma membrane. Instead, these water-soluble hormones interact with a
surface receptor, usually a glycoprotein, and thus, initiate a chain of events
within it. The hormone insulin provides a well-studied example of how this
happens.
The membrane
bound receptors of insulin is a heterotetrameric protein consisting of four
subunits, two -subunits protrude out from surface of the ell and bind insulin,
and two -subunits that span the membrane and protrude into the cytoplasm.
Such
receptors range from fewer than
Binding of
insulin to the outer subunits of the receptor causes a conformational change in
the membrane spanning -subunits, which is also an enzyme, a tyrosine kinase.
The activated -subunits add phosphate groups of specific tyrosine residues
located in cytoplasmic domain of the receptor, as well as a variety of insulin
receptor substrates.
As a result
of -subunit activity, a transducer G protein activates enzyme
phosphodiesterase. This enzyme makes phosphatidylinositol 4,5-biphosphate (PIP2)
into a pair of mediators inositoltriphosphate (IP3) and diacylglycerol
(DG). In turn, IP3, which is water-soluble, and so diffuses into
cytoplasm triggers the release of another messenger Ca2+ ions from
intracellular endoplasmic reticulum activating many calcium-mediated processes.
While DG remains in the membrane where it activates an enzyme called protein
kinase C, which in turn, activates many other enzymes, such as pyruvate
dehydrogenase, and so brings about the physiological effects.
Mediators
amplify the signal in an expanding cascade of response. A single -subunit of
insulin receptor, for example, activates many molecules of DG, and each protein
kinase C molecule activated by DG will, in turn, activate many other enzyme
molecules. DG and IP3 are examples of second messengers,
intermediary compounds that amplify a hormonal signal and so set into action a
variety of events within the affected cell. A variety of events within the
affected cell. A variety of hormones use another second messenger, the cyclic
form of adenosine monophosphate, (cAMP). The enzyme adenylate cyclase
converts adenosine triphosphate (ATP) into cAMP. Because an enzyme can be used
over and over again, a single molecule of active adenylate cyclase can catalyse
production of about 100 molecules of cAMP. In muscle or liver cells, when
hormones, such as, adrenaline bind receptors, the receptors change shape and
bind to G protein, causing it, in turn, to bind the nucleotide guanosine
triphosphate (GTP) and activate another protein adenylate cyclase. The result
of this complex cascade of interactions is the production of large amounts of
cAMP.
cAMP
activates the enzyme protein kinase A, which, in turn, activates the
enzyme phosphorylate kinase. Each molecule of protein kinase A activates
roughly 100 molecules of enzyme, phosphorylate kinase and so on. The net result
is that a single molecule of adrenaline may lead to release of as many as 100
million molecules of glucose within only 1 or 2 minutes. No wonder only very
small quantities of hormone are needed.
Many cells
use more than one second messenger. In heart cells, cAMP serves as a second messenger,
speeding up muscle cell contraction in response to adrenaline, while cyclic
guanosine monophosphate (cGMP) serves as another second messenger, slowing
muscle contraction in response to acetylcholone. It is in this way that the
sympathetic and parasympathetic nervous systems achieve antagonistic effect on
heartbeat. Another example of antagonistic effect is insulin, which lowers
blood sugar level, and glucagons, which raises it.
Another type
of hormonal interaction is known as synergistic effect. Here, two or more
hormones complement each others actions and both are needed for full expression
of the hormone effects. For example, the production, secretion and ejection of
milk by mammary glands require the synergistic effects of estrogens,
progesterone, prolactin and oxytocin.
We have
discussed many dramatic effects of hormone, for instance, testosterone. Yet,
its concentration in the plasma of adult human male is only 30 to 100 ng per
ml. How can hormones in such tiny quantities have such widespread and selective
actions? Unlike catecholamine and peptide hormones, steroid and thyroid
hormones are lipid-soluble hormones and readily pass through the plasma
membrane of a target cell into the cytoplasm. There they bind to specific intracellular
receptor proteins, forming a complex that enters the nucleus and bind to
specific regulatory sites on chromosomes. The binding alters the pattern of
gene expression, initiating the transcription of some genes (DNA), while
repressing the transcription of others. This results in the production of
specific mRNA translation products, proteins and usually enzymes. The actions
of lipid-soluble hormones are slower and last longer than the actions of
water-soluble hormones. These cause physiological responses that are
characteristic of the steroid hormones.
http://www.youtube.com/watch?v=oOj04WsU9ko
Examples of
peptide hormones
Hormones of hypothalamus (releasing
and inhibitory factors), structure, mechanism of action.
Hypothalamus
has the wide anatomic links with other parts of the brain. Therefore in
different mental disorders there is the change of secretion of hypothalamus
hormones.
http://www.youtube.com/watch?v=hLeBNyB1qKU&feature=related
Two
groups of hormones are produced by hypothalamus corresponding to the anterior
and posterior pituitary.
Hypothalamus
and posterior pituitary. 3 peptides are synthesized in the hypothalamus that
pass to the posterior pituitary along axons where they are accumulated:
oxytocin, vasopressin (antidiuretic hormone) and neurophysin. The later binds
the oxytocin and vasopressin and promotes their transportation to the
pituitary.
Hypothalamus
and anterior pituitary. Hypothalamus is connected with the anterior pituitary by
the net of blood capillaries, so called hypothalamic portal system.
Hypothalamus produces very active peptide compounds that pass via this portal
system to anterior pituitary and stimulate or oppress the secretion of tropic
hormones. Compounds stimulating the secretion are called releasing factors. 7
releasing factors are known according to the amount of tropic hormones of
anterior pituitary:
- corticotropin-releasing factor
- thyrotropin-releasing factors
- somatotropin-releasing factors
- follicletropin-releasing factor
- luteotropin-releasing factor
- prolactotropin-releasing factor
- melanotropin-releasing factor.
Hypothalamus
also secretes substances called inhibitory factors or statins, which can
inhibit release of the some pituitary hormones. 3 inhibitory factors are known
today:
- somatostatin
- prolactostatin
- melanostatin.
Releasing
and inhibitory factors are produced in only minute amounts.
http://www.youtube.com/watch?v=-UaSfYKsFh0
Hormones of pituitury, structure,
mechanism of action.
Tropic
hormones are produced by the anterior pituitary. Usually tropic
hormones not directly regulate the metabolism but act on the peripheral
endocrine glands.
|
Somatotropic
hormone (STH, growth hormone)
Chemical
structure: simple protein
The
intensity of secretion is regulated by the relationship between the
somatotropic-releasing factor and somatostatin.
The
main function of somatotropic hormone - stimulation of growth. Hormone is
necessary for the bone tissue formation, for the muscle tissue growth, for the
formation of peculiarities of men and women body.
Somatotropic
hormone can act both directly on the metabolism and indirectly stimulating the
synthesis of somatomedines (specific protein growth factors which are
synthesized in liver).
The effect of somatotropic hormone
on:
- protein metabolism: stimulates the passing of amino acids into
the cells;
activates
the synthesis of proteins, DNA, RNA.
- carbohydrate metabolism: activates the insulinase of liver;
inhibits
the conversion of lipids to carbohydrates;
activates
the exit of glucose from liver;
inhibits
the entry of glucose into the cells.
- lipid metabolism: stimulates lipolisis;
stimulates
the oxidation of fatty acids.
The
deficiency of somatotropic hormone in children age causes nanism. Nanism -
proportional underdevelopment of all body.
The
deficiency of somatotropic hormone in adult persons hasn’t clinical symptoms.
The excess of somatotropic hormone in children age causes gigantism.
The
excess of somatotropic hormone in adult persons causes acromegalia (disproportional development of the separate body
parts).
http://www.youtube.com/watch?v=VX2wgM4kUfM
Thyrotropic hormone (TTH).
Chemical
structure: glicoprotein.
This
hormone is necessary for the normal functions of thyroid glands.
Thyrotropic
hormone promotes:
- accumulation of iodine in thyroid;
- including of iodine into the tyrosine;
- synthesis of thyroxine and triiodothyronine.
Adrenocorticotropic hormone (ACTH).
Chemical
structure: polipeptide.
This
hormone is necessary for the normal functions of adrenal cortex. It enhances
the formation of steroid hormones and their secretion into the blood.
ACTH
has also the melanocyte-stimulating activity.
Excessive
secretion of ACTH causes the Icenko-Kushing disease (symptoms of
hypercorticism, hyperpigmentation).
As
you know, Cushing’s is a rarely diagnosed endocrine disorder characterized by
hypercortisolism. Cortisol is a hormone produced by the adrenal glands and is
vital to regulate the body’s cardivoascular functions and metabolism, to boost
the immune system and to fight inflammation. But its most important job is to
help the body to respond to stress.
The
adrenal glands release cortisol in response to stress, so atheletes, women
experiencing pregnancy, and those suffering from alcoholism, panic disorders
and malnutrition naturally have higher-than-normal levels of cortisol.
People
with Cushing’s Syndrome live life with too much cortisol for their bodies as a
result of a hormone-secreting tumor. Mine is located in the pituitary gland.
Endogenous hypercortisolism leaves the body in a constant state of “fight or
flight,” which ravages the body and tears down the body’s major systems
including cardivascular, musculo-skeletal, endocrine, etc.
Symptoms
vary, but the most common symptoms include rapid, unexplained weight gain in
the upper body with increased fat around the neck and face (“moon facies”);
buffalo hump; facial flushing/plethora; muscle wasting in the arms and legs;
purplish striae (stretch marks) on the abdomen, thighs, buttocks, arms and
breasts; poor wound healing and bruising; severe fatigue; depression, anxiety
disorders and emotional lability; cognitive difficulties; sleep disorders due
to abnormally high nighttime cortisol production; high blood pressure and high
blood sugar/diabetes; edema; vision problems; premature osteoperosis; and, in
women, signs of hyperandrogenism such as menstrual irregularities, infertility,
hirsutism, male-patterned balding and steroid-induced acne.
Most people with Cushing’s long for the ability to do simple things,
like walk a flight of stairs without having to sit for half an hour afterwards,
or vacuum the house or even unload a dishwasher.
One
of the worst parts about this disease is the crushing fatigue and muscle
wasting/weakness, which accompanies hypercortisolism. Not only do we become
socially isolated because of the virilzing effects of an endocrine tumor, which
drastically alters our appearance, but we no longer feel like ourselves with
regard to energy. We would love to take a long bike ride, run three miles or go
shopping like we used to — activities, which we took for granted before the
disease struck. Those activities are sadly impossible at times for those with
advanced stages of the disease.
A patient
with Cushing syndrome showing signs of acne and hirsuitism
Moon face
in patienr with Cushing syndrome
Widened purple striae in a patient with Cushing's
Gonadotropic hormones.
Follicle stimulating hormone
(FSH).
Chemical
structure: glycoprotein.
Function:
stimulates the function of follicles (oogenesis) in women and spermatogenesis
in men.
FSH
(follicle stimulating hormone) regulates the development, growth, pubertal
maturation, and reproductive processes of the body
In both males and females, FSH stimulates the maturation of germ cells.
In males, FSH induces sertoli cells to secrete inhibin and stimulates the
formation of sertoli-sertoli tight junctions (zonula occludens).
In females, FSH initiates follicular growth, specifically affecting granulosa
cells. With the concomitant rise in inhibin B, FSH levels then decline in the
late follicular phase. This seems to be critical in selecting only the most
advanced follicle to proceed to ovulation. At the end of the luteal phase,
there is a slight rise in FSH that seems to be of importance to start the next
ovulatory cycle.
Luteinizing hormone (LH).
Chemical
structure: glycoprotein.
Function:
stimulates the formation of yellow body in women and testosterone secretion in
men.
In
both males and females, (LH) Luteinising hormone is essential for reproduction.
In females, at the time of menstruation, FSH initiates follicular growth,
specifically affecting granulosa cells. With the rise in estrogens, LH
receptors are also expressed on the maturing follicle that produces an
increasing amount of estradiol. Eventually at the time of the maturation of the
follicle, the estrogen rise leads via the 48 hour period.
This
'LH surge' triggers ovulation thereby not only releasing the egg, but also
initiating the conversion of the residual follicle into a corpus luteum that,
in turn, produces progesterone to prepare the endometrium for a possible
implantation. LH is necessary to maintain luteal function for the first two
weeks. In case of a pregnancy luteal function will be further maintained by the
action of hCG (a hormone very similar to LH) from the newly established
pregnancy. LH supports thecal cells in the ovary that provide androgens and
hormonal precursors for estradiol production.
In
the male, LH acts upon the Leydig cells of the testis and is responsible for
the production of testosterone, an androgen that exerts both endocrine activity
and intratesticular activity on spermatogenesis.
Prolactin (PRL).
Chemical
structure: protein.
Functions:
- stimulates lactation;
- stimulates function of yellow body (secretion
of progesterone);
- promotes formation of mother instinct;
- stimulates the formation of prostate glandular
tissue in men.
Lipotropic hormone.
Chemical
structure: protein.
Functions:
- stimulates the mobilization of lipids from depot;
- decreases the Ca amount in blood;
- has the melanocyte-stimulating activity.
Melanocyte
and melanin. |
Posterior pituitary.
Chemical
structure: peptide.
Functions:
- activates the hyaluronidase. This enzyme splits the hyaluronic acid. The
permeability of membranes is increased and reabsorption of water in kidneys is
increased too. As result the day diuresis is decreased;
-
narrows arterioles and capillaries
and increases the blood pressure.
-
-
AVP has two
principle sites of action: the kidney and blood vessels.
-
The primary function of AVP in the
body is to regulate extracellular fluid volume by affecting renal handling of
water, although it is also a vasoconstrictor and pressor agent (hence, the name
"vasopressin"). AVP acts on renal collecting ducts via V2
receptors to increase water permeability (cAMP-dependent mechanism), which
leads to decreased urine formation (hence, the antidiuretic action of
"antidiuretic hormone"). This increases blood volume, cardiac output and
arterial pressure.
-
A secondary function of AVP is
vasoconstriction. AVP binds to V1 receptors on vascular smooth
muscle to cause vasoconstriction via the IP3
signal transduction pathway, which increases arterial
pressure; however, the normal physiological concentrations of AVP are below its
vasoactive range. Studies have shown, nevertheless, that in severe hypovolemic
shock, when AVP release is very high, AVP does contribute to the compensatory
increase in systemic vascular resistance.
The
deficiency of vasopressin in organism causes diabetes insipidus.
Clinical symptoms - poliuria, dehydration of the organism, low density of the
urine.
Diabetes insipidus
results in excessive thirst and urination. The reason is problems with a
particular hormone or its receptor. Diabetes insipidus increases the risk for dehydration.
Diabetes
insipidus is caused by problems related to a hormone called antidiuretic
hormone or its receptor. Antidiuretic hormone (ADH) is produced in a part of
the brain called the hypothalamus. It's stored in the brain's pituitary gland.
Release of ADH causes the kidneys to hold onto water, which makes urine more
concentrated.
Normally, if
we are thirsty or slightly dehydrated, ADH levels rise. The kidneys reabsorb
more water and excrete concentrated urine. If, on the other hand, we chugged a
half-gallon of water (don't try this at home), ADH levels would fall. Clear,
dilute urine would pass. Diabetes insipidus can be caused by either of two
problems with ADH. One is too little ADH is produced. When that's the case, the
condition is called central diabetes insipidus.
The other is there's enough ADH produced, but the kidneys can't respond to it.
That condition is known as nephrogenic diabetes insipidus.
In
either form of diabetes insipidus, the result is the same. The kidneys can't do
their job of conserving water. Even when a person with diabetes insipidus is
dehydrated, the kidneys will excrete abundant, dilute urine. This inability of
the kidneys to conserve water leads to the symptoms of diabetes
insipidus:
In
some people, these symptoms can become extreme, causing dehydration.
Excessive
fluid losses can also cause electrolyte imbalances. Possible symptoms include:
But why
"insipidus?" People with diabetes insipidus aren't insipid, but their
urine is. Insipid can mean dull or lacking flavor. Believe it or not, doctors
long ago would taste urine to detect illness. Unlike diabetes mellitus, which
results in sweet tasting urine, diabetes insipidus creates watery, flavor-free
urine.
Oxytocin.
Chemical
structure: peptide.
Functions:
stimulates the contraction of smooth muscles, especially the muscles of uterus
and muscle fibres of alveoluses of mammas.
Oxytocin
is used for delivery stimulation, for stop of bleeding after delivery, for
stimulation of lactation.
Numerically
the largest group of signaling substances, these arise by protein biosynthesis.
The smallest peptide hormone, thyroliberin (362 Da), is a tripeptide.
Proteohormones can reach masses of more than 20 kDa—e. g., thyrotropin (28
kDa). Similarities in the primary structures of many peptide hormones and
proteohormones show that they are related to one another. They probably arose
from common predecessors in the course of evolution. Thyroliberin (thyrotropin-releasing
hormone, TRH) is one of the neurohormones of the hypothalamus. It stimulates
pituitary gland cells to secrete thyrotropin (TSH). TRH consists of three amino
acids, which are modified in characteristic ways.
Thyrotropin (thyroid-stimulating
hormone, TSH) and the related hormones lutropin (luteinizing hormone,
LH) and follitropin (follicle-stimulating hormone, FSH) originate in the
adenohypophysis. They are all dimeric glycoproteins with masses of around 28
kDa. Thyrotropin stimulates the synthesis and secretion of thyroxin by the
thyroid gland.
Hormones of pancreas,
structure, mechanism of action
Insulin
is produced and released by the B cells of the
pancreas and is released when the glucose level rises. Insulin reduces the
blood sugar level by promoting processes that consume glucose— e. g.,
glycolysis, glycogen synthesis, and conversion of glucose into fatty acids. By
contrast, it inhibits gluconeogenesis and glycogen degradation. Insulin causes
cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal
muscles, glucose is stored as glycogen, and in fat
cells (adipocytes) it is
stored as triglycerides.
Insulin
stops the use of fat as an energy source by inhibiting the release of glucagon. With the
exception of the metabolic disorder diabetes mellitus
and metabolic syndrome,
insulin is provided within the body in a constant proportion to remove excess
glucose from the blood, which otherwise would be toxic. When blood glucose
levels fall below a certain level, the body begins to use stored sugar as an
energy source through glycogenolysis, which
breaks down the glycogen stored in the liver and muscles into glucose, which
can then be utilized as an energy source. As a central metabolic control
mechanism, its status is also used as a control signal to other body systems
(such as amino acid uptake by
body cells). In addition, it has several other anabolic
effects throughout the body.
When control of insulin levels fails, diabetes mellitus can result.
As a consequence, insulin is used medically to treat some forms of diabetes
mellitus. Patients with type 1
diabetes depend on external insulin (most commonly injected
subcutaneously) for their survival because the
hormone is no longer produced internally.[2] Patients
with type 2
diabetes are often insulin resistant
and, because of such resistance, may suffer from a "relative" insulin
deficiency. Some patients with type 2 diabetes may eventually require insulin
if other medications fail to control blood glucose levels adequately. Over 40%
of those with Type 2 diabetes require insulin as part of their diabetes
management plan.
The
human insulin protein is composed of 51 amino acids,
and has a molecular weight of 5808 Da. It is a dimer of an
A-chain and a B-chain, which are linked together by disulfide bonds.
http://www.youtube.com/watch?v=V1LjRi8Nvv4
http://www.youtube.com/watch?v=VLiTbb6MaEU&NR=1
http://www.youtube.com/watch?v=ZsTSoLhl3Y4&feature=related
http://www.youtube.com/watch?v=nBJN7DH83HA&feature=related
Glucagon,
a peptide of 29 amino acids, is a product of the A
cells of the pancreas. It is the antagonist of insulin and, like insulin,
mainly influences carbohydrate and lipid metabolism. Its effects are each
opposite to those of insulin. Glucagon mainly acts via the second messenger
Glucagon is a
linear peptide of 29 amino acids. Its primary sequence is almost perfectly
conserved among vertebrates, and it is structurally related to the secretin
family of peptide hormones. Glucagon is synthesized as proglucagon and
proteolytically processed to yield glucagon within alpha cells of the
pancreatic islets. Proglucagon is also expressed within the intestinal tract,
where it is processed not into glucagon, but to a family of glucagon-like
peptides (enteroglucagon).
The major
effect of glucagon is to stimulate an increase in blood concentration of
glucose. As discussed previously, the brain in particular has an absolute
dependence on glucose as a fuel, because neurons cannot utilize alternative
energy sources like fatty acids to any significant extent. When blood levels of
glucose begin to fall below the normal range, it is imperative to find and pump
additional glucose into blood. Glucagon exerts control over two pivotal
metabolic pathways within the liver, leading that organ to dispense glucose to
the rest of the body:
Glucagon also
appears to have a minor effect of enhancing lipolysis of triglyceride in
adipose tissue, which could be viewed as an addition means of conserving blood
glucose by providing fatty acid fuel to most cells.
Knowing that
glucagon's major effect is to increase blood glucose levels, it makes sense
that glucagon is secreted in response to hypoglycemia or low blood
concentrations of glucose.
Two other
conditions are known to trigger glucagon secretion:
In terms of
negative control, glucagon secretion is inhibited by high levels of blood
glucose. It is not clear whether this reflects a direct effect of glucose on
the alpha cell, or perhaps an effect of insulin, which is known to dampen
glucagon release. Another hormone well known to inhibit glucagon secretion is
somatostatin.
Diseases
associated with excessively high or low secretion of glucagon are rare. Cancers
of alpha cells (glucagonomas) are one situation known to cause excessive
glucagon secretion. These tumors typically lead to a wasting syndrome and,
interestingly, rash and other skin lesions.
Although
insulin deficiency is clearly the major defect in type 1 diabetes mellitus,
there is considerable evidence that aberrant secretion of glucagon contributes
to the metabolic derangements seen in this important disease. For example, many
diabetic patients with hyperglycemia also have elevated blood concentrations of
glucagon, but glucagon secretion is normally suppressed by elevated levels of
blood glucose.
What is
diabetes mellitus?
Diabetes
is a disease of the pancreas, an organ behind your stomach that produces the
hormone insulin. Insulin helps the body use food(glucose) for energy. When a
person has diabetes, the pancreas either cannot produce enough insulin, or the
body uses the insulin incorrectly, or both. Insulin works together with glucose
in the bloodstream to help it enter the body’s cells to be burned for energy.
If the insulin isn’t functioning properly, glucose cannot enter the cells. This
causes glucose levels in the blood to rise, creating a condition of high blood
sugar or hyperglycaemia which is the hallmark of diabetes, and leaving the
cells without fuel. When blood glucose rises above a certain level, it spills
over into the urine.
What are the
common types of diabetes?
There are two
common forms of diabetes: type 1 and type 2.
Generally,
type 2 diabetes is more common in people over age 40 who are overweight.
However, the increased prevalence of obesity has increased the number of people
under age 40 who are diagnosed with type 2 diabetes. Nine out of 10 people with
diabetes have type 2.
What causes
Diabetes Mellitus?
The following
factors may increase your chance of getting diabetes:
How is diabetes
diagnosed?
The preferred
method of diagnosing diabetes is the fasting blood sugar test (FBS). The FBS
measures your blood glucose level after you have fasted (not eaten anything)
for 10 to 12 hours.
Normal
fasting blood glucose is between 70 and 100 mg/dl for people who do not have
diabetes. The
standard diagnosis of diabetes is made when:
Other symptoms may include:
What are some
of the long-term complications of diabetes?
Retinopathy
(eye disease): All patients with diabetes should
see an ophthalmologist (eye specialist) yearly for a dilated eye examination.
Patients with known eye disease, symptoms of blurred vision in one eye or who
have blind spots may need to see their ophthalmologist more frequently.
Nephropathy
(kidney disease): Urine testing should be performed
yearly. Regular blood pressure checks also are important because control of
hypertension (high blood pressure) is essential in slowing kidney disease.
Generally, blood pressure should be maintained less than 130/80 in adults.
Persistent leg or feet swelling also may be a symptom of kidney disease and
should be reported to your doctor.
Neuropathy
(nerve disease): Numbness or tingling in your feet
should be reported to your doctor at your regular visits. You should check your
feet daily for redness, calluses, cracks or breakdown in skin tissue. If you
notice these symptoms before scheduled visits, notify your doctor immediately.
Other
long-term may complications include:
Because of
the link between obesity and type 2 diabetes, you can do a great deal to reduce
your chance of developing the disease by slimming down if you are overweight.
This is especially true if diabetes runs in your family.
In fact, studies
have shown that exercise and a healthy diet can prevent the development of type
2 diabetes in people with impaired glucose tolerance — a condition that often
develops prior to full-blown type 2 diabetes. Medications have also been shown
to provide similar benefit. Both diabetes drugs metformin and Precose have been
shown to prevent the onset of type 2 diabetes in people with this pre-diabetes
condition.
In someone who already has diabetes, exercise and a nutritionally balanced diet
can greatly limit the effects of both types 1 and 2 diabetes on your body. In
diabetics, stopping smoking is one of the best ways to help prevent the
damaging effects of diabetes. If you smoke, quit; smoking dramatically
increases the risk of heart disease, particularly for people with diabetes.
http://www.youtube.com/watch?v=FEsTIOIufiQ
Hormones
of adrenal glands.
Adrenal glands consist of two parts: external -
cortex, internal - medulla.
http://www.youtube.com/watch?v=06jbq3bxKE0&feature=related
Epinephrine is
a hormone synthesized in the adrenal glands from tyrosine. Its release is
subject to neuronal control.This “emergency hormone” mainly acts on the blood
vessels, heart, andmetabolism. It constricts the blood vessels and thereby
increases blood pressure; it increases cardiac function; it promotes the
degradation of glycogen into glucose in the liver and muscles; and it dilates
the bronchia.
Each part secrets specific hormones.
Hormones of adrenal medulla – catecholamines
(epinephrine, norepinephrine, dopamine).
Chemical structure - these hormones are derivatives of
amino acid tyrosine.
Epinephrine, norepinephrine, dopamine exist in blood
in
Functions: causes very potent contraction of vessels
and increase the blood pressure, increase a pulse rate. Epinephrine relaxes the
smooth muscles of bronchi, intestine, promote the contraction of uterus smooth
muscle. Epinephrine play a great role in stress reactions.
Catecholamine, any
of various naturally occurring amines that function as neurotransmitters and hormones within the
body. Catecholamines are characterized by a catechol group (a benzene ring with
two hydroxyl groups) to which is attached an amine (nitrogen-containing) group.
Among the catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine
(noradrenaline).
All
catecholamines are synthesized from the amino acid l-tyrosine
according to the following sequence: tyrosine → dopa
(dihydroxyphenylalanine) → dopamine → norepinephrine
(noradrenaline) → epinephrine
(adrenaline). Catecholamines are synthesized in the brain, in the adrenal medulla, and
by some sympathetic nerve fibres. The particular catecholamine that is
synthesized by a nerve cell, or neuron, depends on
which enzymes are present
in that cell. For example, a neuron that has only the first two enzymes (tyrosine
hydroxylase and dopa decarboxylase) used in the sequence will stop at the
production of dopamine and is called a dopaminergic neuron (i.e., upon
stimulation, it releases dopamine into the synapse). In the
adrenal medulla the enzyme that catalyzes the transformation of norepinephrine
to epinephrine is formed only in the presence of high local concentrations of
glucocorticoids from the adjacent adrenal cortex; chromaffin cells in tissues
outside the adrenal medulla are incapable of synthesizing epinephrine.
l-Dopa is well
known for its role in the treatment of parkinsonism, but its
biological importance lies in the fact that it is a precursor of dopamine, a
neurotransmitter widely distributed in the central nervous system, including
the basal ganglia of the brain (groups of nuclei within the cerebral
hemispheres that collectively control muscle tone, inhibit movement, and
control tremour). A deficiency of dopamine in these ganglia leads to
parkinsonism, and this deficiency is at least partially alleviated by the
administration of l-dopa.
Under
ordinary circumstances, more epinephrine than norepinephrine is released from
the adrenal medulla. In contrast, more norepinephrine is released from the sympathetic nervous system
elsewhere in the body. In physiological terms, a major action of the hormones
of the adrenal medulla and the sympathetic nervous system is to initiate a
rapid, generalized fight-or-flight response.
This response, which may be triggered by a fall in blood pressure or by pain, physical injury, abrupt
emotional upset, or hypoglycemia, is
characterized by an increased heart rate (tachycardia), anxiety, increased
perspiration, tremour, and increased blood glucose concentrations (due to glycogenolysis, or
breakdown of liver glycogen). These
actions of catecholamines occur in concert with other neural or hormonal
responses to stress, such as
increases in adrenocorticotropic hormone
(ACTH) and cortisol secretion.
Furthermore,
the tissue responses to different catecholamines depend on the fact that there
are two major types of adrenergic receptors
(adrenoceptors) on the surface of target organs and tissues. The receptors are
known as alpha-adrenergic and beta-adrenergic receptors, or alpha receptors and beta receptors,
respectively. In general, activation of alpha-adrenergic receptors results in
the constriction of blood vessels, contraction
of uterine muscles, relaxation of intestinal muscles, and dilation of the pupils. Activation of
beta-adrenergic receptors increases heart rate and stimulates cardiac
contraction (thereby increasing cardiac output), dilates the bronchi (thereby
increasing air flow into and out of the lungs), dilates the blood vessels,
and relaxes the uterus. Drugs that
block the activation of beta receptors (beta blockers), such as
propranolol, are often given to patients with tachycardia, high blood pressure,
or chest pain (angina pectoris). These
drugs are contraindicated in patients with asthma because they worsen bronchial
constriction.
Catecholamines
play a key role in nutrient metabolism and the generation of body heat
(thermogenesis). They stimulate not only oxygen consumption but also
consumption of fuels, such as glucose and free fatty acids, thereby
generating heat. They stimulate glycogenolysis and the breakdown of triglycerides, the stored
form of fat, to free fatty acids (lipolysis). They also have a role in the
regulation of secretion of multiple hormones. For example, dopamine inhibits prolactin secretion,
norepinephrine stimulates gonadotropin-releasing hormone
secretion, and epinephrine inhibits insulin secretion by
the beta cells of the islets of Langerhans
of the pancreas.
The effect of epinephrine on carbohydrate metabolism:
- activates
the decomposition of glycogen in liver and muscles;
- activates
the glycolysis, Krebs cycle and tissue respiration;
- causes
the hyperglycemia.
The effect of
epinephrine on protein metabolism:
- activates
the protein decomposition.
The effect of epinephrine on lipid metabolism:
-
activates the tissue lipase,
mobilization of lipids and oxidation of fatty acids.
-
Norepinephrine (NE) and epinephrine
(E) are both sympathomimetic catecholamines that are synthesized in the adrenal
medulla and terminals of sympathetic neurons. Along the metabolic pathway, NE
is synthesized first -- and when an enzyme adds a methyl group, you have
epinephrine. NE is the main catecholamine in peripheral tissue and sympathetic
neurons. E is
mostly made in the adrenal medulla.
-
http://www.youtube.com/watch?v=4g25d7_Afmc
Tissue hormones
Hormonoids
(tissue hormones, histohormones) - organic trace substances produced by different
cells of different tissues (not by specific glands) that regulate metabolism on
the local level (some hormonoids are
produced in the blood too (serotonin, acetylcholine).
In
the organs, the hormones carry out physiological and biochemical regulatory
functions. In contrast to endocrine hormones, tissue hormones are only
active in the immediate vicinity of the cells that secrete them. The
distinctions between hormones and other signaling substances (mediators,
neurotransmitters, and growth factors) are fluid. Mediators is the term
used for signaling substances that do not derive from special hormone- forming
cells, but are formbymany cell types. Acetylcholine
is a neurotransmitter. What that does is it releases
chemicals into the brain and plays a role in normal brain
functions such as sleep. Also, it deals with attention, learning, and memory
skills. The mechanisms that the transmitter controls was a mystery until now.
Scientist now know that acetycholine deals with communication between neurons.
Located in the prefrontal cortex. This is the formula for acetylcholine.
When
acetylcholine is released it binds to a specific reactor. Next it begins to
start a molecule cascade. Which then triggers physiological alterations. Which
deals with how prefrontal cortical neurons are “wired” together. This
explains how acethlcholine is released into the brain. This process
may actually have an effect in the formation of new associative memories. Most
of this information can be found in the artical on acetylchonline.
The Professor of Cellular Neuroscience, Zafar Bashir was the one who
demonstrated how electron stimulation of the prefrontal cortex leads to the
release of acetylcholine. Then Dr. Douglas Caruana carried out another
experiment. He also found that acetylchonline when released into the prefrontal
cortex it helps you remember things. But when to much has been released those
memories start to be forgotten.
Just like the
article said in the Journal of Neuroscience. Acetylcholine is a
neurotransmitter which plays key roles in sleep and other normal functions.
This is basically what acetylcholine does before of course we found out that to
much of it is dangerous.
Gastrin is released
in response to certain stimuli. These include:
Gastrin
release is inhibited by:
The
presence of gastrin stimulates parietal cells of the
stomach to secrete hydrochloric acid
(HCl)/gastric acid. This is done both directly on the parietal cell and
indirectly via binding onto CCK2/gastrin
receptors on ECL cells
in the stomach, which then responds by releasing histamine,
which in turn acts in a paracrine manner on parietal cells stimulating them to
secrete H+ ions. This is the major stimulus for acid secretion by parietal
cells.
Along with
the above mentioned function, gastrin has been shown to have additional
functions as well:
Heparin, a highly-sulfated glycosaminoglycan, is widely used
as an injectable anticoagulant and has the highest negative charge density of
any known biological molecule; it consists of a variably-sulfated repeating
disaccharide unit: The most common disaccharide unit is composed of a
2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine, IdoA-GlcN
Heparin is a
naturally-occurring anticoagulant produced by basophils and mast cells;
pharmaceutical grade heparin is derived from mucosal tissues of slaughtered
meat animals such as porcine intestine or bovine lung. Heparin allows the
body's natural clot lysis mechanisms to work normally to break down clots that
have already formed.
Heparin
binds to the enzyme inhibitor antithrombin (AT) causing
a conformational change that results in its activation through an increase in
the flexibility of its reactive site loop. The activated AT then inactivates thrombin
and other proteases involved in blood clotting, most notably factor
Xa. The rate of inactivation of these proteases by AT
can increase by up to 1000-fold due to the binding of heparin.
The conformational change inAT on heparin-binding
mediates its inhibition of factor Xa. For thrombin inhibition however, thrombin
must also bind to the heparin polymer at a site proximal to the pentasaccharide.
The highly-negative charge density of heparin contributes to its very strong
electrostatic interaction with thrombin The formation of a ternary complex
between AT, thrombin, and heparin results in the
inactivation of thrombin. For this reason heparin's activity against thrombin
is size-dependent, the ternary complex requiring at least 18 saccharide units
for efficient formation. In contrast anti factor Xa activity only requires the
pentasaccharide binding site
This size difference has led to the development of low-molecular-weight heparins
and more recently to fondaparinux as pharmaceutical
anticoagulants. Low-molecular-weight heparins and fondaparinux target
anti-factor Xa activity rather than anti-thrombin (IIa) activity, with the aim
of facilitating a more subtle regulation of coagulation and an improved
therapeutic index
Secretin
hormone production is stimulated by acid chyme entering the duodenum. This
hormone stimulates the pancreas to release bicarbonate to
neutralize the acid.
Secretin is a hormone that both
controls the environment in the duodenum
by regulating secretions of the stomach and pancreas, and
regulates water homeostasis throughout
the body. It is produced in the S cells of the
duodenum, which are located in the crypts of
Lieberkühn. In humans, the secretin peptide is
encoded by the SCT gene. Secretin was also the first
hormone to be identified.
Secretin
regulates the pH within the duodenum by
inhibiting gastric acid secretion by
the parietal cells of the
stomach, and by stimulating bicarbonate production
by the centroacinar cells and
intercalated ducts of the pancreas.
In 2007,
secretin was discovered to play a role in osmoregulation
by acting on the hypothalamus, pituitary, and kidney.
Secretin
increases watery bicarbonate solution from pancreatic and bile duct epithelium.
Pancreatic centroacinar cells have secretin receptors in their plasma membrane.
As secretin binds to these receptors, it stimulates adenylate cyclase activity
and converts ATP to cyclic AMP.
Cyclic AMP acts as second messenger in intracellular signal transduction and
leads to increase in release of watery carbonate. It is known to promote the
normal growth and maintenance of the pancreas.
Secretin
increases water and bicarbonate secretion from duodenal Brunner's glands
to buffer the incoming protons of the acidic chyme. It also enhances the effects of cholecystokinin
to induce the secretion of digestive enzymes and bile from pancreas
and gallbladder,
respectively.
It
counteracts blood glucose
concentration spikes by triggering increased insulin
release from pancreas, following oral glucose
intake.
Although
secretin releases gastrin from gastrinomas,
it inhibits gastrin release from the normal stomach. It reduces acid secretion
from the stomach
by inhibiting gastrin
release from G cells.
This helps neutralize the pH of the digestive products entering the duodenum
from the stomach, as digestive enzymes
from the pancreas (e.g., pancreatic amylase and pancreatic lipase)
function optimally at slightly basic pH.
In addition,
secretin stimulates pepsin secretion from chief cells, which can
help break down proteins in food digestion. It stimulates release of glucagon, pancreatic polypeptide
and somatostatin.
Histamine, an important mediator (local
signaling substance) and neurotransmitter, is mainly stored in tissue
mast cells and basophilic granulocytes in the blood. It is involved in
inflammatory and allergic reactions. “Histamine liberators” such as tissue
hormones, type E immunoglobulins (see p. 300), and drugs can release it.
Histamine acts via various types of receptor. Binding to H1 receptors promotes
contraction of smoothmuscle in the bronchia, and dilates the capillary vessels
and increases their permeability. Via H2 receptors, histamine slows down the
heart rate and promotes the formation of HCl in the gastric mucosa. In the
brain, histamine acts as a neurotransmitter.
They
have hormone-like effects in their immediate surroundings. Histamine and
prostaglandins are important examples of these substances. Histamine is
found in plant and animal tissue and is released from mast cells as part of an
allergic reaction in humans. Release of histamine stimulates gastric secretion
and causes dilation of capillaries, constriction of bronchial smooth muscle,
and decreases blood pressure.
Histamines are released from mast cells as an allergic response to
abnormal proteins found in the blood. The mast cells are found in connective
tissue that contains numerous basophilic granules and releases substances such
as heparin and histamine in response to injury or inflammation of body tissues.
How severe
can histamine reactions be?
It has recently
been discovered that histamines may play a much larger roll in human disease
than once thought. In the past, histamine production was blamed on some very
common allergic reactions such as hay fever, bee sting reactions, and
anaphylactic shock.
In
recent studies, histamine involvement in chronic inflammatory and degenerative
diseases such as Lupus, Arthritis, Gulf War Syndrome, Fibromyalgia, Leaky Gut
Syndrome, and some skin disorders like Psoriasis and obscure Rashes, has come
to light as causes of chronic inflammatory responses to abnormal proteins in
the blood of chronically ill patients!
Histamine is a biogenic amine
involved in local immune responses as well as regulating physiological function
in the gut and acting as a neurotransmitter. Histamine triggers the
inflammatory response. As part of an immune response to foreign pathogens,
histamine is produced by basophils and by mast cells found in nearby connective
tissues. Histamine increases the permeability of the capillaries to white blood
cells and other proteins, in order to allow them to engage foreign invaders in
the affected tissues. It is found in virtually all animal body cells.
Histamine
forms colorless hygroscopic crystals that melt at
Histamine has two basic centres, namely the aliphatic
amino group and whichever nitrogen atom of the imidazole ring does not already
have a proton. Under physiological conditions, the aliphatic amino group
(having a pKa around 9.4) will be protonated, whereas the second
nitrogen of the imidazole ring (pKa ≈ 5.8) will not be
protonated. Thus, histamine is normally protonated to a singly-charged cation.
Histamine is derived from the decarboxylation of the amino acid histidine, a
reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic
vasoactive amine.
Once
formed, histamine is either stored or rapidly inactivated. Histamine released
into the synapses is broken down by acetaldehyde dehydrogenase. It is the
deficiency of this enzyme that triggers an allergic
reaction as histamines pool in the synapses. Histamine is broken down by
histamine-N-methyltransferase and diamine oxidase. Some forms of foodborne
disease, so-called "food poisonings," are due to conversion of
histidine into histamine in spoiled food, such as fish.
Serotonin is a neurotransmitter
=
Neurotransmitters are chemicals that are used to relay, amplify and
modulate signals between a neuron and another cell - cell to cell communicators
=
Serotonin is produced in the body from amino acids
=
Serotonin taken orally does not pass into the serotonergic pathways of
the central nervous system because it does not cross the blood-brain barrier.
However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which
serotonin is synthesized, can and does cross the blood-brain barrier. These
agents are available as dietary supplements and may be effective serotonergic agents
=
Drugs may hinder the natural use/loss of serotonin but Drugs do not
incease the supply of serotonin.
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine
neurotransmitter. Biochemically derived from tryptophan, serotonin
is primarily found in the gastrointestinal
(GI) tract, platelets, and in the central
nervous system (CNS) of animals including humans.
It is popularly thought to be a contributor to feelings of well-being and happiness.
Approximately
90% of the human body's total serotonin is
located in the enterochromaffin
cells in the alimentary canal (gut), where it
is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons of the CNS,
where it has various functions. These include the regulation of mood,
appetite, and sleep. Serotonin also has some cognitive functions, including
memory and learning. Modulation of serotonin at synapses is thought to be a
major action of several classes of pharmacological antidepressants.
Serotonin secreted from the enterochromaffin cells
eventually finds its way out of tissues into the blood. There, it is actively
taken up by blood platelets, which store
it. When the platelets bind to a clot, they disgorge serotonin, where it serves
as a vasoconstrictor and helps to
regulate hemostasis and blood
clotting. Serotonin also is a growth factor for some types of cells, which may
give it a role in wound healing.