Gastrin is a
peptide hormone that stimulates secretion of
gastric acid (HCl) by the
parietal cells of the
stomach and aids in gastric motility. It is released by
G cells in the
pyloric antrum of the stomach,
duodenum, and the
pancreas
The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
.
Gastrin binds to
cholecystokinin B receptor
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the ''CCKBR'' gene.
This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin (CCK), regulatory peptides of the brain and g ...
s to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K
+/H
+ ATPase pumps into the apical membrane of parietal cells (which in turn increases H
+ release into the stomach cavity). Its release is stimulated by
peptides
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...
in the
lumen of the stomach.
Physiology
Genetics
In humans, the ''GAS'' gene is located on the long arm of the
seventeenth chromosome (17q21).
Synthesis
Gastrin is a linear
peptide hormone produced by
G cells of the duodenum and in the
pyloric antrum of the
stomach. It is secreted into the bloodstream. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in
posttranslational modification to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:
* ''
gastrin-34'' ("
big gastrin")
* ''
gastrin-17'' ("
little gastrin")
* ''
gastrin-14'' ("
minigastrin")
Also,
pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
end of gastrin.
The numbers refer to the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
count.
Release
Gastrin is released in response to certain stimuli. These include:
*
stomach antrum distension
*
vagal
The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
stimulation (mediated by the
neurocrine bombesin, or
GRP in humans)
* the presence of partially
digested protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s, especially
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.
*
hypercalcemia (via
calcium-sensing receptors)
Gastrin release is inhibited by:
* the presence of
acid
An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...
(primarily the secreted HCl) in the stomach (a case of
negative feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...
)
*
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
also inhibits the release of gastrin, along with
secretin, GIP (
gastroinhibitory peptide), VIP (
vasoactive intestinal peptide),
glucagon and
calcitonin.
Function
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 respond by releasing
histamine
Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
, 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:
* Stimulates parietal cell maturation and fundal growth.
* Causes
chief cells to secrete
pepsinogen, the
zymogen (inactive) form of the digestive
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
pepsin.
* Increases antral muscle mobility and promotes stomach contractions.
* Strengthens antral contractions against the pylorus, and relaxes the pyloric sphincter, which increases the rate of gastric emptying.
* Plays a role in the relaxation of the
ileocecal valve In many Animalia, including humans, an ileocolic structure or problem is something that concerns the region of the gastrointestinal tract from the ileum to the large intestine, colon. In Animalia that have cecum, ceca, the ileocecal region is a sub ...
.
* Induces
pancreatic secretions and
gallbladder emptying.
* May impact
lower esophageal sphincter (LES) tone, causing it to contract,
- although pentagastrin, rather than endogenous gastrin, may be the cause.
* Gastrin contributes to the
gastrocolic reflex.
Factors influencing secretion
Factors influencing secretion of gastrin can be divided into 2 categories:
Physiologic
=Gastric lumen
=
* Stimulatory factors: dietary protein and amino acids (meat),
hypercalcemia. (i.e. during the gastric phase)
* Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from
δ cells in the stomach, which inhibits gastrin and histamine release.
=Paracrine
=
* Stimulatory factor:
bombesin or
gastrin-releasing peptide (GRP)
* Inhibitory factor:
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
- acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.
=Nervous
=
* Stimulatory factors:
Beta-adrenergic agents,
cholinergic agents,
gastrin-releasing peptide (GRP)
* Inhibitory factor:
Enterogastric reflex
=Circulation
=
* Stimulatory factor: gastrin
* Inhibitory factors:
gastric inhibitory peptide (GIP),
secretin,
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
,
glucagon,
calcitonin
Pathophysiologic
=Paraneoplastic
=
* Gastrinoma
paraneoplastic oversecretion (see ''
Role in disease'')
Role in disease
In the
Zollinger–Ellison syndrome, gastrin is produced at excessive levels, often by a
gastrinoma gastrin-producing tumor, mostly benign of the
duodenum or the
pancreas
The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
. To investigate for hypergastrinemia high blood levels of gastrin, a "
pentagastrin test" can be performed.
In autoimmune
gastritis, the immune system attacks the
parietal cells leading to
hypochlorhydria low stomach acid secretion. This results in an elevated gastrin level in an attempt to compensate for increased pH in the stomach. Eventually, all the parietal cells are lost and
achlorhydria results leading to a loss of
negative feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused ...
on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with
mucolipidosis type IV (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder.
Additionally, elevated gastrin levels may be present in chronic gastritis resulting from ''H. pylori'' infection.
History
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by
Hilda Tracy and
Roderic Alfred Gregory at the
University of Liverpool
The University of Liverpool (abbreviated UOL) is a Public university, public research university in Liverpool, England. Founded in 1881 as University College Liverpool, Victoria University (United Kingdom), Victoria University, it received Ro ...
.
In 1964 the structure of gastrin was determined.
References
Further reading
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External links
Overview at colostate.edu*
{{Neuropeptides
Peptide hormones
Gastric hormones
Digestive system
Cholecystokinin agonists