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14-September-2008 18:02:46 - Gastrin Gastrin Identifiers Symbols 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 CG cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it. CG cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it. In humans, gastrin is a hormone that stimulates secretion of gastric acid HCl by the parietal cells of the stomach, as well as aiding in gastric motility. 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,12 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 Physiology Genetics The GAS gene is located on the long arm of the seventeenth chromosome 17q21.4 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. 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, GIPgastroinhibitory peptide, VIP, glucagon and calcitonin. 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. 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 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. References ^ Edkins JS 1906. The chemical mechanism of gastric secretion. J. Physiol. Lond. 34 1-2: 133-44. PMID 16992839. PMC:1465807. ^ Modlin IM, Kidd M, Marks IN, Tang LH 1997. The pivotal role of John S. Edkins in the discovery of gastrin. World J Surg 21 2: 226-34. doi:10.1007/s002689900221. PMID 8995084. ^ Gregory RA, Tracy HJ 1964. The constitution and properties of two gastrins extracted from hog antral mucosa. Gut 5: 103-14. doi:10.1136/gut.5.2.103. PMID 14159395. PMC:1552180. ^ Lund T, Geurts van Kessel AH, Haun S, Dixon JE 1986. The genes for human gastrin and cholecystokinin are located on different chromosomes. Hum. Genet. 73 1: 77-80. doi:10.1007/BF00292669. PMID 3011648. Further reading Rozengurt E, Walsh JH 2001. Gastrin, CCK, signaling, and cancer. Annu. Rev. Physiol. 63: 49-76. doi:10.1146/annurev.physiol.63.1.49. PMID 11181948. Dockray GJ 2005. Clinical endocrinology and metabolism. Gastrin. Best Pract. Res. Clin. Endocrinol. Metab. 18 4: 555-68. doi:10.1016/j.beem.2004.07.003. PMID 15533775. Anlauf M, Garbrecht N, Henopp T, et al. 2006. Sporadic versus herary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J. Gastroenterol. 12 34: 5440-6. PMID 17006979. Polosatov MV, Klimov PK, Masevich CG, et al. 1979. Interaction of synthetic human big gastrin with blood proteins of man and animals. Acta hepato-gastroenterologica 26 2: 154-9. PMID 463490. Fritsch WP, Hausamen TU, Scholten T 1977. Gastrointestinal hormones. I. Hormones of the gastrin group. Zeitschrift für Gastroenterologie 15 4: 264-76. PMID 871064. Higashimoto Y, Himeno S, Shinomura Y, et al. 1989. Purification and structural determination of urinary NH2-terminal big gastrin fragments. Biochem. Biophys. Res. Commun. 160 3: 1364-70. doi:10.1016/S0006-291X8980154-8. PMID 2730647. Pauwels S, Najdovski T, Dimaline R, et al. 1989. Degradation of human gastrin and CCK by endopeptidase 24.11: differential behaviour of the sulphated and unsulphated peptides. Biochim. Biophys. Acta 996 1-2: 82-8. PMID 2736261. Lund T, Geurts van Kessel AH, Haun S, Dixon JE 1986. The genes for human gastrin and cholecystokinin are located on different chromosomes. Hum. Genet. 73 1: 77-80. doi:10.1007/BF00292669. PMID 3011648. Kariya Y, Kato K, Hayashizaki Y, et al. 1987. Expression of human gastrin gene in normal and gastrinoma tissues. Gene 50 1-3: 345-52. PMID 3034736. Gregory RA, Tracy HJ, Agarwal KL, Grossman MI 1969. Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue. Gut 10 8: 603-8. doi:10.1136/gut.10.8.603. PMID 5822140. Bentley PH, Kenner GW, Sheppard RC 1967. Structures of human gastrins I and II. Nature 209 5023: 583-5. PMID 5921183. Ito R, Sato K, Helmer T, et al. 1984. Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence. Proc. Natl. Acad. Sci. U.S.A. 81 15: 4662-6. doi:10.1073/pnas.81.15.4662. PMID 6087340. Wiborg O, Berglund L, Boel E, et al. 1984. Structure of a human gastrin gene. Proc. Natl. Acad. Sci. U.S.A. 81 4: 1067-9. doi:10.1073/pnas.81.4.1067. PMID 6322186. Kato K, Hayashizaki Y, Takahashi Y, et al. 1984. Molecular cloning of the human gastrin gene. Nucleic Acids Res. 11 23: 8197-203. PMID 6324077. Boel E, Vuust J, Norris F, et al. 1983. Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc. Natl. Acad. Sci. U.S.A. 80 10: 2866-9. doi:10.1073/pnas.80.10.2866. PMID 6574456. Kato K, Himeno S, Takahashi Y, et al. 1984. Molecular cloning of human gastrin precursor cDNA. Gene 26 1: 53-7. PMID 6689486. Koh TJ, Wang TC 1995. Molecular cloning and sequencing of the murine gastrin gene. Biochem. Biophys. Res. Commun. 216 1: 34-41. doi:10.1006/bbrc.1995.2588. PMID 7488110. Rehfeld JF, Hansen CP, Johnsen AH 1995. Post-polyGlu cleavage and degradation modified by O-sulfated tyrosine: a novel post-translational processing mechanism. EMBO J. 14 2: 389-96. PMID 7530658. Rehfeld JF, Johnsen AH 1994. Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product. Eur. J. Biochem. 223 3: 765-73. doi:10.1111/j.1432-1033.1994.tb19051.x. PMID 8055952. Varro A, Dockray GJ 1993. Post-translational processing of progastrin: inhibition of cleavage, phosphorylation and sulphation by brefeldin A. Biochem. J. 295 Pt 3: 813-9. PMID 8240296. 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 - Enterohepatic circulation 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 Retrieved from http://en..org/wiki/Gastrin Categories: Genes on chromosome 17 | Human proteins | Peptide hormones | Gastric hormones | Digestive systemHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Þ‹Þ¨ÞˆÞ¬Þ€Þ¨Þ„Þ¦Þ?Þ° Español Français Italiano עברית Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português РуÑ?Ñ?кий СрпÑ?ки / Srpski Suomi Svenska ä¸æ–‡ This page was last modified on 8 July 2008, at 00:39
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