Gastrin

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Gastrin
Identifiers
Symbol(s)	GAST; GAS
External IDs	OMIM: 137250 MGI: 104768 HomoloGene: 628
Gene ontology Molecular Function: • hormone activity Cellular Component: • extracellular region • soluble fraction Biological Process: • smooth muscle contraction • signal transduction
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	2520	14459
Ensembl	ENSG00000184502	ENSMUSG00000017165
Uniprot	P01350	Q6GSF5
Refseq	NM_000805 (mRNA) NP_000796 (protein)	NM_010257 (mRNA) NP_034387 (protein)
Location	Chr 17: 37.12 - 37.13 Mb	Chr 11: 100.15 - 100.15 Mb
Pubmed search	[1]	[2]

In humans, gastrin is a hormone that stimulates secretion of gastric acid by the parietal cells of the stomach. It is released by G cells in the stomach and duodenum. Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,^[1][2] and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool.^[3]

Contents 1 Physiology 1.1 Genetics 1.2 Synthesis 1.3 Release 1.4 Function 1.5 Factors influencing secretion 2 Role in disease 3 References 4 Further reading 5 External links

[edit] Physiology

[edit] Genetics

The GAS gene is located on the long arm of the seventeenth chromosome (17q21).^[4]

[edit] 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:

• gastrin-34 ("big gastrin")
• gastrin-17 ("little gastrin")
• gastrin-14 ("minigastrin")

The numbers refer to the amino acid count.

[edit] Release

Gastrin is released in response to certain stimuli. These include:

• stomach distension
• vagal stimulation (mediated by the neurocrine bombesin, or GRP in the human)
• the presence of partially digested proteins especially amino acids
• hypercalcemia

Gastrin release is inhibited by:

• 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, glucagon and calcitonin.

[edit] Function

The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done 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 ECL cells.

Direct binding of gastrin to the parietal cells is involved in parietal cell maturation and fundal growth.

Gastrin also causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin. Pepsinogen is converted to pepsin in a low pH environment, and the HCl provides a suitable environment for its activity. It can also increase antral muscle mobility and trophic effect on GI tract and causes promotion of contraction of circular muscle of the stomach. In digestion, gastrin strengthens the antral contractions against the pylorus, and constricts the pyloric sphincter, which has the effect of slowing the rate of gastric emptying.

Gastrin has also been shown to induce production of pancreatic enzymes by acinar cells.

It increases gastric blood flow.

[edit] Factors influencing secretion

Gastric lumen:

• Stimulatory factors: dietary protein and amino acids, 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:

• Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)

Circulation:

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

[edit] 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 pyloric antrum or the pancreas. 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 acidity). This results in an elevated gastrin level in an attempt to compensate for low acidity. Eventually, all the parietal cells are lost and achlorhydria results leading to a loss of negative feedback on gastrin secretion.

[edit] References

[edit] Further reading

[edit] External links

• Overview at colostate.edu
• Physiology at MCG 6/6ch4/s6ch4_14

v • d • e Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones) Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin) Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone (T3 and T4) - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy) Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2) Target-derived NGF, BDNF, NT-3

v • d • e Digestive system, physiology: gastrointestinal physiology Enteric nervous system Meissner's plexus - Auerbach's plexus Exocrine Chief cells (Pepsinogen) - Parietal cells (Gastric acid, Intrinsic factor) - Goblet cells (Mucus) Endocrine/paracrine G cells (gastrin), D cells (somatostatin) - ECL cells (Histamine) - enterogastrone: I cells (CCK), K cells (GIP), S cells (secretin), Enteroendocrine cells Border Brunner's glands - Paneth cells - Enterocytes Fluids Saliva - Bile - Intestinal juice - Gastric juice - Pancreatic juice Processes Swallowing - Vomiting - Peristalsis (Interstitial cell of Cajal) - Migrating motor complex - Borborygmus - Gastrocolic reflex - Segmentation contractions - Defecation

v • d • e Hormones: gastrointestinal hormones CCK - EGF - GIP - Gastrin releasing peptide - Gastrins - Proglucagon - Motilin - Peptide YY -Prokineticin - Secretin - VIP

v • d • e Peptides: neuropeptides Hypothalamic Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC (ACTH, MSH, Lipotropin) Gastrointestinal hormones Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide Other hormones Vasopressin - Calcitonin - Other Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins (Bradykinin, Tachykinins ) - Neuromedin (B, N, U) - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide