Gastrin is a
peptide hormone that stimulates secretion of
gastric acid
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the ...
(HCl) by the
parietal cells of the
stomach and aids in gastric motility. It is released by
G cell
In anatomy, the G cell or gastrin cell, is a type of cell in the stomach and duodenum that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells. G cells are found deep within the pyloric glands of the stomach antru ...
s in the
pyloric antrum of the stomach,
duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
, and the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
.
Gastrin binds to
cholecystokinin B receptors 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. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
...
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 cell
In anatomy, the G cell or gastrin cell, is a type of cell in the stomach and duodenum that secretes gastrin. It works in conjunction with gastric chief cells and parietal cells. G cells are found deep within the pyloric glands of the stomach antru ...
s 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
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
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, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein i ...
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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
count.
Release
Gastrin is released in response to certain stimuli. These include:
*
stomach antrum distension
*
vagal 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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, especially
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.
*
hypercalcemia
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...
(via
calcium-sensing receptors)
Gastrin release is inhibited by:
* the presence of
acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
(primarily the secreted HCl) in the stomach (a case of
negative feedback)
*
somatostatin also inhibits the release of gastrin, along with
secretin, GIP (
gastroinhibitory peptide), VIP (
vasoactive intestinal peptide
Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the lig ...
),
glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to tre ...
and
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
.
Function
The presence of gastrin stimulates
parietal cells of the stomach to
secrete hydrochloric acid
Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dige ...
(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
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...
, 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
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the activ ...
(inactive) form of the digestive
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
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.
* 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
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...
. (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 - 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,
glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to tre ...
,
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
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
Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duod ...
gastrin-producing tumor, mostly benign of the
duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
or the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
. 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 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
, mottoeng = These days of peace foster learning
, established = 1881 – University College Liverpool1884 – affiliated to the federal Victoria Universityhttp://www.legislation.gov.uk/ukla/2004/4 University of Manchester Act 200 ...
.
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