Secretin

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Secretin
Identifiers
SymbolSCT
External IDsOMIM182099 MGI99466 HomoloGene7928 GeneCards: SCT Gene
Orthologs
SpeciesHumanMouse
Entrez634320287
EnsemblENSG00000070031ENSMUSG00000038580
UniProtP09683Q08535
RefSeq (mRNA)NM_021920NM_011328
RefSeq (protein)NP_068739NP_035458
Location (UCSC)Chr 11:
0.63 – 0.63 Mb
Chr 7:
141.28 – 141.28 Mb
PubMed search[1][2]
 
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Secretin
Identifiers
SymbolSCT
External IDsOMIM182099 MGI99466 HomoloGene7928 GeneCards: SCT Gene
Orthologs
SpeciesHumanMouse
Entrez634320287
EnsemblENSG00000070031ENSMUSG00000038580
UniProtP09683Q08535
RefSeq (mRNA)NM_021920NM_011328
RefSeq (protein)NP_068739NP_035458
Location (UCSC)Chr 11:
0.63 – 0.63 Mb
Chr 7:
141.28 – 141.28 Mb
PubMed search[1][2]

Secretin is a hormone that regulates water homeostasis throughout the body, and influences the environment of the duodenum by regulating secretions in the stomach and pancreas. Secretin is produced in the S cells of the duodenum, which are located in the crypts of Lieberkühn.[1] In humans, the secretin peptide is encoded by the SCT gene.[2] Secretin was the first hormone to be identified.[3]

Secretin also helps regulate the pH of the duodenum by: inhibiting the secretion of gastric acid from the parietal cells of the stomach; and stimulating the production of bicarbonate from the centroacinar cells and intercalated ducts of the pancreas.[4]

In 2007, secretin was discovered to play a role in osmoregulation by acting on the hypothalamus, pituitary, and kidney.[5][6]

Discovery[edit]

In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion.[7] It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter 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[edit]

Secretin is initially synthesized as a 120 amino acid precursor protein known as prosecretin. This precursor contains an N-terminal signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid C-terminal peptide.[2]

The mature secretin peptide 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.[8]

Secretin also has an amidated carboxyl-terminal amino acid which is valine.[9] The sequence of amino acids in secretin is H–His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val–NH2.[9]

Physiology[edit]

Production[edit]

Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the mucosa of the duodenum, and in smaller numbers in the jejunum of the small intestine.[10]

Stimulus[edit]

Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species.[11] Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.[12]

The 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 causes 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 in the small intestine and preventing acid burns.[13] Other factors are involved in the release of secretin such as bile salts and fatty acids, which result in additional bicarbonates being added to the small intestine.[14] Secretin release is inhibited by H2 antagonists, which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released.[15]

Function[edit]

Secretin increases watery bicarbonate solution from pancreatic and bile duct epithelium. Pancreatic centroacinar 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.[16] 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 to buffer the incoming protons of the acidic chyme.[17] 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.[18]

Although secretin releases gastrin from gastrinomas, it inhibits gastrin release from the normal stomach. It reduces acid secretion from the stomach by inhibiting gastrin release from G cells.[19]:844 This helps neutralize the pH of the digestive products entering the duodenum from the stomach, as digestive enzymes from the pancreas (e.g., pancreatic amylase and pancreatic lipase) function optimally at slightly basic pH.[citation needed]

In addition, secretin stimulates pepsinogen secretion from chief cells, which can help break down proteins in food digestion. It stimulates release of glucagon, pancreatic polypeptide and somatostatin.[11]

Uses[edit]

Secretin has been widely used in medical field especially in pancreatic functioning test because it increases pancreatic secretions. Secretin is either injected[20] or given through a tube that is inserted through nose, stomach then duodenum.[21] This test can provide information about 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; as yet there is no evidence to support it as effective.[22][23]

Osmoregulation[edit]

Secretin modulates water and electrolyte transport in pancreatic duct cells,[24] liver cholangiocytes,[25] and epididymis epithelial cells.[26] It is found[27] to play a role in the vasopressin-independent regulation of renal water reabsorption.[5]

Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus and along the neurohypophysial tract to neurohypophysis. During increased osmolality, it is released from the posterior pituitary. In the hypothalamus, it activates vasopressin release.[6] It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release.[28]

It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).[6] In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found.[6] 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."[6]

Food intake[edit]

Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the paraventricular nucleus and the arcuate nucleus, which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating an anorectic role of the peptide. This function of the peptide is mediated by the central melanocortin system.[29]

See also[edit]

References[edit]

  1. ^ Häcki WH (September 1980). "Secretin". Clin Gastroenterol 9 (3): 609–32. PMID 7000396. 
  2. ^ a b 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): 2299–2303. doi:10.1073/pnas.87.6.2299. PMC 53674. PMID 2315322. 
  3. ^ http://www.ncbi.nlm.nih.gov/pubmed/11816326
  4. ^ 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. 
  5. ^ a b Chu JY, Chung SC, Lam AK, Tam S, Chung SK, Chow BK (April 2007). "Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption". Mol. Cell. Biol. 27 (7): 2499–2511. doi:10.1128/MCB.01088-06. PMC 1899889. PMID 17283064. 
  6. ^ a b c d e Chu JY, Lee LT, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BK (September 2009). "Secretin as a neurohypophysial factor regulating body water homeostasis". Proc. Natl. Acad. Sci. U.S.A. 106 (37): 15961–15966. doi:10.1073/pnas.0903695106. PMC 2747226. PMID 19805236. 
  7. ^ Bayliss W, Starling EH (1902). "The mechanism of pancreatic secretion". J. Physiol. (London) 28: 325–353. 
  8. ^ Williams, Robert L. (1981). Textbook of Endocrinology. Philadelphia: Saunders. p. 697. ISBN 0-7216-9398-9. 
  9. ^ a b DeGroot, Leslie Jacob (1989). J. E. McGuigan, ed. Endocrinology. Philadelphia: Saunders. p. 2748. ISBN 0-7216-2888-5. 
  10. ^ 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): 739–744. doi:10.3109/00365527109179946. PMID 4945081. 
  11. ^ 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. p. 1326. ISBN 0-07-022001-8. 
  12. ^ William F. Ganong, MD (2003). "26. Regulation of Gastrointestinal Function". Review of Medical Physiology (Twenty-First ed.). New York: McGraw-Hill, Medical Pub. Div. ISBN 0-07-140236-5. 
  13. ^ http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/secretin.html
  14. ^ 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): 180–184. doi:10.1136/gut.19.3.180. PMC 1411891. PMID 631638. 
  15. ^ 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): 591–597. doi:10.1007/BF01367670. PMID 7249893. 
  16. ^ Gardner JD (1978). "Receptors and gastrointestinal hormones". In Sleisenger MH, Fordtran JS. Gastrointestinal Disease (2nd ed.). Philadelphia: WB Saunders Company. 
  17. ^ Hall, John E.; Guyton, Arthur C. (2006). Textbook of medical physiology. St. Louis, Mo: Elsevier Saunders. pp. 800–801. ISBN 0-7216-0240-1. 
  18. ^ 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): 524–529. doi:10.1172/JCI106262. PMC 322500. PMID 5415678. 
  19. ^ Palmer KR, Penman ID (2010). "Alimentary track and pancreatic disease". In Colledge NR, Walker BR, Ralston SH. Davidson's Principles and Practice of Medicine (20th ed.). Edinburgh: Churchill Livingstone. ISBN 0-7020-3085-6. 
  20. ^ "Human Secretin". Patient Information Sheets. United States Food and Drug Administration. 2004-07-13. Retrieved 2008-11-01. [dead link]
  21. ^ "Secretin stimulation test". MedlinePlus Medical Encyclopedia. United States National Library of Medicine. Retrieved 2008-11-01. 
  22. ^ "The Use of Secretin to Treat Autism". NIH News Alert. United States National Institutes of Health. 1998-10-16. Retrieved 2008-11-30. 
  23. ^ Sandler, A. D.; Sutton, K. A.; Deweese, J.; Girardi, M. A.; Sheppard, V.; Bodfish, J. W. (1999). "Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder". New England Journal of Medicine 341 (24): 1801–1806. doi:10.1056/NEJM199912093412404. PMID 10588965.  edit
  24. ^ Villanger O, Veel T, Raeder MG (March 1995). "Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase". Gastroenterology 108 (3): 850–859. doi:10.1016/0016-5085(95)90460-3. PMID 7875488. 
  25. ^ Marinelli RA, Pham L, Agre P, LaRusso NF (May 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): 12984–12988. doi:10.1074/jbc.272.20.12984. PMID 9148905. 
  26. ^ Chow BK, Cheung KH, Tsang EM, Leung MC, Lee SM, Wong PY (June 2004). "Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion". Biol. Reprod. 70 (6): 1594–1599. doi:10.1095/biolreprod.103.024257. PMID 14749298. 
  27. ^ Cheng CY, Chu JY, Chow BK (September 2009). "Vasopressin-independent mechanisms in controlling water homeostasis". J. Mol. Endocrinol. 43 (3): 81–92. doi:10.1677/JME-08-0123. PMID 19318428. 
  28. ^ Lee VH, Lee LT, Chu JY, Lam IP, Siu FK, Vaudry H, Chow BK (December 2010). "An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II". FASEB J. 24 (12): 5024–32. doi:10.1096/fj.10-165399. PMC 2992369. PMID 20739612. 
  29. ^ Cheng CY, Chu JY, Chow BK (January 2011). "Central and peripheral administration of secretin inhibits food intake in mice through the activation of the melanocortin system". Neuropsychopharmacology 36 (2): 459–71. doi:10.1038/npp.2010.178. PMC 3055665. PMID 20927047. 

Further reading[edit]

External links[edit]