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Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Secretin helps regulate the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate from the centroacinar cells and intercalated ducts of the pancreas. It also stimulates bile production by the liver; the bile emulsifies dietary fats in the duodenum so that pancreatic lipase can act upon them. Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, cholecystokinin, is stimulating the gallbladder to contract, delivering its stored bile for the same reason.
Prosecretin is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by gastric acid in the lower intestine to neutralize the pH and ensure no damage is done to the small intestine by the aforementioned acid.
Secretin was the first hormone to be identified. In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion. 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.
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.
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.
Secretin also has an amidated carboxyl-terminal amino acid which is valine. 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.
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. Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine.
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 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. 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. 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.
Secretin stimulates the release of a watery bicarbonate solution from the 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. Cyclic AMP acts as second messenger in intracellular signal transduction and leads to an increase in the release of watery bicarbonate. 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. It also enhances the effects of cholecystokinin to induce the secretion of digestive enzymes and bile from pancreas and gallbladder, respectively.
Although secretin releases gastrin from gastrinomas, it inhibits gastrin release from the normal stomach. It reduces acid secretion by parietal cells of the stomach. It does this through at least three mechanisms: 1) By stimulating release of somatostatin, 2) By inhibiting release of gastrin in the pyloric antrum, and 3) By direct downregulation of the parietal cell acid secretory mechanics. 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.
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.
Secretin has been widely used in medical field especially in pancreatic functioning test because it increases pancreatic secretions. Secretin is either injected or given through a tube that is inserted through nose, stomach then duodenum. This test can provide information about whether there are any abnormalities in the pancreas which can include gastrinoma, pancreatitis or pancreatic cancer.
Secretin modulates water and electrolyte transport in pancreatic duct cells, liver cholangiocytes, and epididymis epithelial cells. It is found to play a role in the vasopressin-independent regulation of renal water reabsorption.
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. 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.
It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of aquaporin 2, or both are found. 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."
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.
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