Gastrin is a
peptide hormone
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
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
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the ...
of the
stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
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 antrum ...
s in the
pyloric antrum
The pylorus ( or ), or pyloric part, connects the stomach to the duodenum. The pylorus is considered as having two parts, the ''pyloric antrum'' (opening to the body of the stomach) and the ''pyloric canal'' (opening to the duodenum). The ''pylori ...
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 end ...
.
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. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
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
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
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 antrum ...
s of the duodenum and in the
pyloric antrum
The pylorus ( or ), or pyloric part, connects the stomach to the duodenum. The pylorus is considered as having two parts, the ''pyloric antrum'' (opening to the body of the stomach) and the ''pyloric canal'' (opening to the duodenum). The ''pylori ...
of the
stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
. 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 ribosome ...
to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:
* ''
gastrin-34
Big gastrin (G-34) is a form of gastrin with 34 amino acids in its sequence. Big gastrin is a hormone produced by G cells and can be found inside of the stomach. G-34 promotes the secretion of gastric acid in dogs. In dogs, the half life of this ...
'' ("
big gastrin
Big gastrin (G-34) is a form of gastrin with 34 amino acids in its sequence. Big gastrin is a hormone produced by G cells and can be found inside of the stomach. G-34 promotes the secretion of gastric acid in dogs. In dogs, the half life of this ...
")
* ''
gastrin-17
Little gastrin I is a form of gastrin
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 s ...
'' ("
little gastrin
Little gastrin I is a form of gastrin commonly called as gastrin-17. This is a protein hormone, secreted by the intestine.
Gastrin II has identical amino acid composition to Gastrin I, the only difference is that the single tyrosine residue is s ...
")
* ''
gastrin-14
Minigastrin (also mini gastrin) is a form of gastrin. Its sequence is H-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2.
Minigastrin has shown to be a potential therapeutic agent for thyroid carcinoma by targeting cancer-promoting cholecy ...
'' ("
minigastrin
Minigastrin (also mini gastrin) is a form of gastrin. Its sequence is H-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2.
Minigastrin has shown to be a potential therapeutic agent for thyroid carcinoma by targeting cancer-promoting cholecy ...
")
Also,
pentagastrin
Pentagastrin (trade name Peptavlon) is a synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid as the pentagast ...
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 is ...
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 am ...
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, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right v ...
stimulation (mediated by the
neurocrine bombesin
Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad (''Bombina bombina'')
by Vittorio Erspamer ''et al.'' and named after its source. NIHMSID 45053. It has two known homologs in mammals called ...
, 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, respo ...
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 hypercalcemi ...
(via
calcium-sensing receptor
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney and the brain. In the parathyroid ...
s)
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 sequ ...
(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 by ...
)
*
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...
also inhibits the release of gastrin, along with
secretin
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...
, GIP (
gastroinhibitory peptide
Glucose-dependent insulinotropic polypeptide (GIP), also known as Gastric inhibitory polypeptide or gastric inhibitory peptide (also abbreviated as GIP), is an releasing and inhibiting hormones, inhibiting hormone of the secretin family of hormone ...
), 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 ligan ...
),
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 Glucagon (medicati ...
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 cell
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the ...
s of the stomach to
secrete 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
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
Acid strength is the tendency of an acid, symbol ...
(HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding onto
CCK2/gastrin receptors on
ECL cells
Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell found in the gastric glands of the gastric mucosa beneath the epithelium, in particular in the vicinity of parietal cells, that aid in the production of gastric acid via th ...
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 discovered in ...
, 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 In human anatomy, there are three types of chief cells, the gastric chief cell, the parathyroid chief cell, and the type 1 chief cells found in the carotid body.
Cell types
The gastric chief cell (also known as a zymogenic cell or peptic cell) is a ...
to secrete
pepsinogen
Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, whe ...
, 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 active ...
(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. A ...
pepsin
Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, w ...
.
* 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
The ileocecal valve (ileal papilla, ileocaecal valve, Tulp's valve, Tulpius valve, Bauhin's valve, ileocecal eminence, valve of Varolius or colic valve) is a sphincter muscle valve that separates the small intestine and the large intestine. Its c ...
.
* Induces
pancreatic
The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...
secretions and
gallbladder
In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
emptying.
* May impact
lower esophageal sphincter
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
(LES) tone, causing it to contract,
- although pentagastrin, rather than endogenous gastrin, may be the cause.
* Gastrin contributes to the
gastrocolic reflex
The gastrocolic reflex or gastrocolic response is a physiological reflex that controls the motility, or peristalsis, of the gastrointestinal tract following a meal. It involves an increase in motility of the colon consisting primarily of giant mi ...
.
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 hypercalcemi ...
. (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
Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad (''Bombina bombina'')
by Vittorio Erspamer ''et al.'' and named after its source. NIHMSID 45053. It has two known homologs in mammals called ...
or
gastrin-releasing peptide
Gastrin-releasing peptide, also known as GRP, is a neuropeptide, a regulatory molecule that has been implicated in a number of physiological and pathophysiological processes. Most notably, GRP stimulates the release of gastrin from the G cells of ...
(GRP)
* Inhibitory factor:
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...
- 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
Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine in ...
agents,
cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
agents,
gastrin-releasing peptide
Gastrin-releasing peptide, also known as GRP, is a neuropeptide, a regulatory molecule that has been implicated in a number of physiological and pathophysiological processes. Most notably, GRP stimulates the release of gastrin from the G cells of ...
(GRP)
* Inhibitory factor:
Enterogastric reflex
The enterogastric reflex is one of the three extrinsic reflexes of the gastrointestinal tract, the other two being the gastroileal reflex and the gastrocolic reflex. The enterogastric reflex is stimulated by duodenal distension. It can also be s ...
=Circulation
=
* Stimulatory factor: gastrin
* Inhibitory factors:
gastric inhibitory peptide
Glucose-dependent insulinotropic polypeptide (GIP), also known as Gastric inhibitory polypeptide or gastric inhibitory peptide (also abbreviated as GIP), is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor ...
(GIP),
secretin
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...
,
somatostatin
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...
,
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 Glucagon (medicati ...
,
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
A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
oversecretion (see ''
Role in disease'')
Role in disease
In the
Zollinger–Ellison syndrome
Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea.
The syndrome is caused by a gastrinoma, a neuroendocrin ...
, 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 end ...
. To investigate for hypergastrinemia high blood levels of gastrin, a "
pentagastrin
Pentagastrin (trade name Peptavlon) is a synthetic polypeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid as the pentagast ...
test" can be performed.
In autoimmune
gastritis
Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possi ...
, the immune system attacks the
parietal cells
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the ...
leading to
hypochlorhydria
Achlorhydria and hypochlorhydria refer to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low, respectively. It is associated with various other medical problems.
Sign ...
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
Achlorhydria and hypochlorhydria refer to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low, respectively. It is associated with various other medical problems.
Sign ...
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 by ...
on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with
mucolipidosis type IV
Mucolipidosis type IV (ML IV, ganglioside sialidase deficiency, or ML4) is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberration ...
(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
Roderic Alfred Gregory CBE FRS (29 December 1913 – 5 September 1990) was a British physiologist.
He was born in 1913 in Plaistow, Essex, the only child of Alfred Gregory and Alice Jane (née Greaves) Gregory. His father was a fitter and turn ...
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