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Secretin
Identifiers
Symbol SCT
Entrez 6343
HUGO 10607
OMIM 182099
RefSeq NM_021920
UniProt P09683
Other data
Locus Chr. 11 p15.5

Secretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn.[1] Its effect is to regulate the pH of the duodenal contents via the control of gastric acid secretion and buffering with bicarbonate. It is notable for being the first hormone to be identified. In humans, the secretin peptide is encoded by the SCT gene.[2][3]

It has recently been discovered to play a role in osmoregulation in the hypothalamus, pituitary, and kidney.[4][5]

Contents

Discovery

In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion.[6] It was known that the pancreas secreted digestive juices in response to the passage of food into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion secretin. Secretin was the first such "chemical messenger" identified. This type of substance is now called a hormone, a term coined by Bayliss in 1905.

Structure

Secretin is a linear peptide hormone, which is composed of 27 amino acids and has a molecular weight of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of glucagon, vasoactive intestinal peptide (VIP), and gastric inhibitory peptide (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP.[7]

Secretin also has an amidated carboxyl-terminal amino acid which is valine.[8] The sequence of amino acids in secretin is:

Physiology

Production

Secretin is synthesized in cytoplasmic secretory granules of S-cells which are found mainly in mucosa of duodenum, and smaller numbers in jejunum of small intestine.[9]

Stimulus

Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 4 and 4.5 depending on species.[10]

It is the active form of prosecretin. This acidity is due to hydrochloric acid in the chyme that enters the duodenum from the stomach via the pyloric sphincter. Secretin targets the pancreas, which cause the organ to secrete a bicarbonate-rich fluid that flows into the intestine. Bicarbonate ion is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes to the small intestine and preventing acid burns[11] Other factors are also involved in the release of secretin such as bile salts and fatty acids, which result in additional bicarbonates being added to the small intestine.[12] Secretin release is inhibited by H2 receptor antagonists, which reduce gastric acid secretion. As a result, the pH in the duodenum increases above 4.5, and secretin cannot be released.[13]

Function

Secretin stimulates the secretion of bile from the liver. It also increases watery bicarbonate solution from pancreatic duct epithelium. Pancreatic acinar cells have secretin receptors in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts ATP to cyclic AMP.[14] Cyclic AMP acts as second messenger in intracellular signal transduction and leads to increase in release of watery carbonate.It is known to promote the normal growth and maintenance of the pancreas.

Secretin increases water and bicarbonate secretion from duodenal Brunner's glands in order to buffer the incoming protons of the acidic chyme.[15] It also enhances the effects of cholecystokinin to induce the secretion of digestive enzymes and bile from pancreas and gallbladder, respectively.

It counteracts blood glucose concentration spikes by triggering increased insulin release from pancreas, following oral glucose intake.<[16]

It also reduces acid secretion from the stomach by inhibiting gastrin release from G cells.[citation needed] This helps neutralize the pH of the digestive products entering the duodenum from the stomach, as digestive enzymes from the pancreas (eg, pancreatic amylase and pancreatic lipase) function optimally at slightly basic pH.[citation needed]

In addition, secretin stimulates pepsin secretion, which can help break down proteins in food digestion. It also stimulates release of glucagon, pancreatic polypeptide and somatostatin.[10]

Uses

Secretin has been widely used in medical field especially in pancreatic functioning test. Secretin is either injected[17] or given through the tube that is inserted through nose, stomach then duodenum.[18] This test can provide information whether there are any abnormalities in pancreas which can be gastrinoma, pancreatitis or pancreatic cancer.

Secretin has been proposed as a possible treatment for autism based on a hypothetical gut-brain connection, but as yet there is no evidence to support it as effective.[19]

Osmoregulation

Secretin modulates water and electrolyte transport in pancreatic duct cells,[20] liver cholangiocytes,[21] and epididymis epithelial cells.[22] It has also been recently been found to play a role in the vasopressin-independent regulation of renal water reabsorption.[4]

Secretin is found in the hypothalamus and neurohypophysis, During increased osmoalality it is released from the posterior pituitary. In the hypothalamus, it activates vasopressin release.[5]

It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D Syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).[5] In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found.[5] It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades."[5]

References

  1. ^ Häcki WH (September 1980). "Secretin". Clin Gastroenterol 9 (3): 609–32. PMID 7000396. 
  2. ^ Kopin AS, Wheeler MB, Leiter AB (March 1990). "Secretin: structure of the precursor and tissue distribution of the mRNA". Proc. Natl. Acad. Sci. U.S.A. 87 (6): 2299–303. doi:10.1073/pnas.87.6.2299. PMID 2315322. PMC 53674. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2315322. 
  3. ^ Whitmore TE, Holloway JL, Lofton-Day CE, Maurer MF, Chen L, Quinton TJ, Vincent JB, Scherer SW, Lok S (2000). "Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA". Cytogenet. Cell Genet. 90 (1-2): 47–52. doi:10.1159/000015658. PMID 11060443. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=ccg90047. 
  4. ^ a b Chu JY, Chung SC, Lam AK, Tam S, Chung SK, Chow BK. (2007). Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption. Mol Cell Biol. 27(7):2499-511. PMID 17283064
  5. ^ a b c d e Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK.(2009). Secretin as a neurohypophysial factor regulating body water homeostasis. Proceedings of the National Academy of Sciences USA, 106:15961–15966. doi:10.1073/pnas.0903695106
  6. ^ Bayliss W, Starling EH (1902). "The mechanism of pancreatic secretion". J. Physiol. (London) 28: 325–353. 
  7. ^ Williams, Robert L. (1981). Textbook of Endocrinology. Philadelphia: Saunders. pp. 697. ISBN 0-7216-9398-9. 
  8. ^ a b DeGroot, Leslie Jacob (1989). J. E. McGuigan. ed. Endocrinology. Philadelphia: Saunders. pp. 2748. ISBN 0-7216-2888-5. 
  9. ^ Polak JM, Coulling I, Bloom S, Pearse AG (1971). "Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa". Scandinavian Journal of Gastroenterology 6 (8): 739–44. PMID 4945081. 
  10. ^ a b Frohman, Lawrence A.; Felig, Philip (2001). "Gastrointestinal Hormones and Carcinoid Syndrome". in P. K. Ghosh and T. M. O’Dorisio. Endocrinology & metabolism. New York: McGraw-Hill, Medical Pub. Div. pp. 1326. ISBN 0-07-022001-8. 
  11. ^ http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/secretin.html
  12. ^ Osnes M, Hanssen LE, Flaten O, Myren J (March 1978). "Exocrine pancreatic secretion and immunoreactive secretin (IRS) release after intraduodenal instillation of bile in man". Gut 19 (3): 180–4. doi:10.1136/gut.19.3.180. PMID 631638. PMC 1411891. http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=631638. 
  13. ^ Rominger JM, Chey WY, Chang TM (July 1981). "Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases". Digestive diseases and sciences 26 (7): 591–7. doi:10.1007/BF01367670. PMID 7249893. 
  14. ^ Gardner JD (1978). "Receptors and gastrointestinal hormones". in Sleisenger MH, Fordtran JS. Gastrointestinal Disease (2nd ed.). Philadelphia: WB Saunders Company. 
  15. ^ Hall, John E.; Guyton, Arthur C. (2006). Textbook of medical physiology. St. Louis, Mo: Elsevier Saunders. pp. 800–801. ISBN 0-7216-0240-1. 
  16. ^ Kraegen EW, Chisholm DJ, Young JD, Lazarus L (March 1970). "The gastrointestinal stimulus to insulin release. II. A dual action of secretin". J. Clin. Invest. 49 (3): 524–9. doi:10.1172/JCI106262. PMID 5415678. 
  17. ^ "Human Secretin". Patient Information Sheets. United States Food and Drug Administration. 2004-07-13. http://www.fda.gov/cder/consumerinfo/druginfo/Human_Secretin.HTM. Retrieved 2008-11-01. 
  18. ^ "Secretin stimulation test". MedlinePlus Medical Encyclopedia. United States National Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/003892.htm#Definition. Retrieved 2008-11-01. 
  19. ^ "The Use of Secretin to Treat Autism". NIH News Alert. United States National Institutes of Health. 1998-10-16. http://www.nichd.nih.gov/news/releases/secretin.cfm. Retrieved 2008-11-30. 
  20. ^ Villanger O, Veel T, Raeder MG. (1995). Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase. Gastroenterology. 108(3):850-9. PMID 7875488
  21. ^ Marinelli RA, Pham L, Agre P, LaRusso NF. (1997). Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane. Evidence for a secretin-induced vesicular translocation of aquaporin-1. J Biol Chem. 272(20):12984-8. PMID 9148905
  22. ^ Chow BK, Cheung KH, Tsang EM, Leung MC, Lee SM, Wong PY. (2004). Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion. Biol Reprod. 70(6):1594-9. PMID 14749298

See also

External links








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