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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

* * * * * * * * * * * * * * * * * * * *


External links


Overview at colostate.edu
* {{Neuropeptides Peptide hormones Gastric hormones Digestive system Cholecystokinin agonists