Structural Biochemistry/Secretin

Secretin is a hormone that controls secretions into the duodenum and water homeostasis in the body. It is first produced in the S cells in the duodenum during the crypts of Lieberkuhn. Bayliss W, Starling EH The mechanism of pancreatic secretion J. Physiol. (London) 28 325–353 1902 Secretin works by regulating the pH of duodenal by controlling gastric acid secretion and buffering by utilizing the bicarbonate found in centroacinar cells in the pancreas. DeGroot, Leslie Jacob J. E. McGuigan Endocrinology Saunders Philadelphia 1989 2748 0-7216-2888-5 It is also noted to be the first hormone to be identified. Polak JM, Coulling I, Bloom S, Pearse AG Immunofluorescent localization of secretin and enteroglucagon in human intestinal mucosa Scandinavian Journal of Gastroenterology 6 8 739–744 1971 4945081 10.3109/00365527109179946 The secretin protein in the human genome is encoded by the SCT Gene. Gardner JD Sleisenger MH, Fordtran JS Gastrointestinal Disease 2nd WB Saunders Company Philadelphia 1978 Receptors and gastrointestinal hormones Discovery During the 1900s, Ernest Starling and William Bayliss were studying how the human nervous system controls how the body digests food. Villanger O, Veel T, Raeder MG Secretin causes H+/HCO3- secretion from pig pancreatic ductules by vacuolar-type H(+)-adenosine triphosphatase Gastroenterology 108 3 850–859 1995 March 7875488 10.1016/0016-5085(95)90460-3 It was already known that the pancreas helped during the digestion by secreting juices to help pass food through the pyloric sphincter into the duodenum. Starling and Bayliss discovered that this process was not controlled by the pancreas but by the nervous system. They did this by first cutting all of the nerves to the pancreases in their model animals and observing how the digestive system responded. Starling and Bayliss determined that the substance that was secreted during digestion by the intestinal lining initiated the pancreas secretion through the bloodstream. They named this this secretion secretin, being the first chemical messenger identified. These types of substances were called hormones, a term Bayliss coined in 1905. Structure Secretin was synthesized as a 120 amino acid precursor protein also known as prosecretin. Prosecretin contains an n-terminus, secretin, spacer, and a c-terminus. Secretin is a linear peptide that is made up out of 27 different amino acids with a molecular weight of 3055. It also forms an alpha-helical structure between the 5 and 13th amino acid positions. Some of the amino acid sequences present in secretin have similarities of those amino acids in glyucagon, gastric inhibitory peptide (GIP) and vasoactive intestinal peptide (VIP). Fourteen out of the twenty-seven amino acids in secretin are in the same positions in the protein glucagon, 10 in GIP, and 7 in VIP. Marinelli RA, Pham L, Agre P, LaRusso NF 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 1997 May 9148905 10.1074/jbc.272.20.12984 http://www.jbc.org/content/272/20/12984.full.pdf Function Secretin works by increasing the bicarbonate concentration in the pancreas. The pancreas contains centroacinar cells that have secretin receptors located on their plasma membrane. When secretin binds to the receptors on the membrane, it initiates adenylate cyclase activity and converts cyclic AMP from ATP.Cyclic AMP is a second messenger in intracellular signal transduction and increases the concentration of carbonate. It is also known to promote the growth and maintenance of the pancreas. Secretin increases water and bicarbonate secretion in the duodenal to buffer incoming protons of the acidic chyme. In addition, it also enhances the effects of cholecystokinin to produce secretion of digestive enzymes from the gallbladder and pancreas. It also decreases the blood glucose concentration by increasing insulin being released by the pancreas. In addition, secretin stimulates pepsin secretion from chief cells, which then help break down proteins during digestion. It also stimulates the release of glycagon, somatostatin, and pancreatic polypeptide. Chow BK, Cheung KH, Tsang EM, Leung MC, Lee SM, Wong PY Secretin controls anion secretion in the rat epididymis in an autocrine/paracrine fashion Biol. Reprod. 70 6 1594–1599 2004 June 14749298 10.1095/biolreprod.103.024257 References 30em