Gastrin

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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.

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 in the lumen of the stomach.

PhysiologyEdit

GeneticsEdit

In humans, the GAS gene is located on the long arm of the seventeenth chromosome (17q21).<ref>Template:Cite journal</ref>

SynthesisEdit

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:

Also, pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the C-terminus end of gastrin. The numbers refer to the amino acid count.

ReleaseEdit

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 proteins, especially amino acids, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.<ref>Template:Cite book</ref>
hypercalcemia (via calcium-sensing receptors<ref>Template:Cite journal</ref>)

Gastrin release is inhibited by:<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

the presence of acid (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), glucagon and calcitonin.

FunctionEdit

File:Control-of-stomach-acid-sec.png

G cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it. Note: this diagram does not illustrate gastrin's stimulatory effect on ECL cells.

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, 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.<ref>Template:Cite journal</ref>

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 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.<ref>Template:Cite book</ref>
Plays a role in the relaxation of the ileocecal valve.<ref name="pmid9430795">Template:Cite journal</ref>
Induces pancreatic secretions and gallbladder emptying.<ref name="pmid950091">Template:Cite journal</ref>
May impact lower esophageal sphincter (LES) tone, causing it to contract,<ref name="pmid626547">Template:Cite journal</ref> - although pentagastrin, rather than endogenous gastrin, may be the cause.<ref name="pmid631634">Template:Cite journal</ref>
Gastrin contributes to the gastrocolic reflex.

Factors influencing secretionEdit

Factors influencing secretion of gastrin can be divided into 2 categories:<ref>Template:Cite book</ref>

PhysiologicEdit

Gastric lumenEdit

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.

ParacrineEdit

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.

NervousEdit

Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)
Inhibitory factor: Enterogastric reflex

CirculationEdit

Stimulatory factor: gastrin
Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin

PathophysiologicEdit

ParaneoplasticEdit

Gastrinoma paraneoplastic oversecretion (see Role in disease)

Role in diseaseEdit

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. To investigate for hypergastrinemia high blood levels of gastrin, a "pentagastrin test" can be performed.<ref>Template:Cite book</ref>

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.<ref name="pmid9448310">Template:Cite journal</ref> Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H. pylori infection.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

HistoryEdit

Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and gastrins were isolated in 1964 by Hilda Tracy and Roderic Alfred Gregory at the University of Liverpool.<ref>Template:Cite journal</ref> In 1964 the structure of gastrin was determined.<ref name="pmid14248711">Template:Cite journal</ref>

ReferencesEdit

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External linksEdit

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