Gastrin

From Infogalactic: the planetary knowledge core
Jump to: navigation, search

<templatestyles src="Module:Infobox/styles.css"></templatestyles>

Gastrin
Identifiers
Symbols GAST ; GAS
External IDs OMIM137250 MGI1098667 HomoloGene628 GeneCards: GAST Gene
RNA expression pattern
PBB GE ADAM11 207880 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2520 14459
Ensembl ENSG00000184502 ENSMUSG00000017165
UniProt P01350 P48757
RefSeq (mRNA) NM_000805 NM_010257
RefSeq (protein) NP_000796 NP_034387
Location (UCSC) Chr 17:
41.71 – 41.72 Mb
Chr 11:
100.33 – 100.34 Mb
PubMed search [1] [2]
Gastrin
Identifiers
Symbol Gastrin
Pfam PF00918
InterPro IPR001651
PROSITE PDOC00232

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.

Physiology

Genetics

The GAS gene is located on the long arm of the eighteenth chromosome (17q21).[1]

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. Gastrin is found primarily in three forms:

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.

Release

Gastrin is released in response to certain stimuli. These include:[citation needed]

Gastrin release is inhibited by:[3][4]

Function

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 then responds 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.[citation needed]

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 constricts the pyloric sphincter, which diminishes the rate of gastric emptying.
  • Plays a role in the relaxation of the ileocecal valve.[5]
  • Induces pancreatic secretions and gallbladder emptying.[6]
  • May impact lower esophageal sphincter (LES) tone, causing it to contract,[7] - although pentagastrin, rather than endogenous gastrin, may be the cause.[8]

Factors influencing secretion

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
  • 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

Circulation

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. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.[citation needed]

In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acidity). 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.[9]

History

Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[10][11] and gastrins were isolated in 1964 by Roderic Alfred Gregory at the University of Liverpool.[12] In 1964 the structure of Gastrin was determined.[13]

References

  1. Lua error in package.lua at line 80: module 'strict' not found.
  2. Lua error in package.lua at line 80: module 'strict' not found.
  3. Lua error in package.lua at line 80: module 'strict' not found.
  4. Lua error in package.lua at line 80: module 'strict' not found.
  5. Lua error in package.lua at line 80: module 'strict' not found.
  6. Lua error in package.lua at line 80: module 'strict' not found.
  7. Lua error in package.lua at line 80: module 'strict' not found.
  8. Lua error in package.lua at line 80: module 'strict' not found.
  9. Lua error in package.lua at line 80: module 'strict' not found.
  10. Lua error in package.lua at line 80: module 'strict' not found.
  11. Lua error in package.lua at line 80: module 'strict' not found.
  12. Lua error in package.lua at line 80: module 'strict' not found.
  13. Lua error in package.lua at line 80: module 'strict' not found.

Further reading

  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.

External links