Secretin

Secretin is a peptide is_associated_with::hormone that regulates water homeostasis throughout the body, and influences the environment of the is_associated_with::duodenum by regulating secretions in the is_associated_with::stomach and is_associated_with::pancreas. Secretin is produced in the is_associated_with::S cells of the duodenum, which are located in the is_associated_with::intestinal glands. In humans, the secretin peptide is encoded by the SCT is_associated_with::gene. Secretin was the first hormone to be identified.

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

In 2007, secretin was discovered to play a role in is_associated_with::osmoregulation by acting on the is_associated_with::hypothalamus, is_associated_with::pituitary, and is_associated_with::kidney.

Discovery
In 1902, is_associated_with::William Bayliss and is_associated_with::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 is_associated_with::hormone, a term coined by Bayliss in 1905.

Structure
Secretin is initially synthesized as a 120 amino acid precursor protein known as is_associated_with::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 is_associated_with::peptide hormone, which is composed of 27 is_associated_with::amino acids and has a is_associated_with::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 is_associated_with::glucagon, is_associated_with::vasoactive intestinal peptide (VIP), and is_associated_with::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 is_associated_with::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.

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

Stimulus
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 is_associated_with::hydrochloric acid in the is_associated_with::chyme that enters the duodenum from the stomach via the is_associated_with::pyloric sphincter. Secretin targets the is_associated_with::pancreas, which causes the organ to secrete a bicarbonate-rich fluid that flows into the is_associated_with::intestine. is_associated_with::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.

Function
Secretin stimulates the release of a watery bicarbonate solution from the pancreatic and bile duct epithelium. Pancreatic centroacinar cells have is_associated_with::secretin receptors in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts ATP to is_associated_with::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 is_associated_with::pancreas.

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

It counteracts is_associated_with::blood glucose concentration spikes by triggering increased is_associated_with::insulin release from pancreas, following oral is_associated_with::glucose intake.

Although secretin releases gastrin from is_associated_with::gastrinomas, it inhibits gastrin release from the normal stomach. It reduces acid secretion by is_associated_with::parietal cells of the is_associated_with::stomach. It does this through at least three mechanisms: 1) By stimulating release of is_associated_with::somatostatin, 2) By inhibiting release of is_associated_with::gastrin in the is_associated_with::pyloric antrum, and 3) By direct is_associated_with::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 is_associated_with::enzymes from the pancreas (e.g., is_associated_with::pancreatic amylase and is_associated_with::pancreatic lipase) function optimally at slightly basic pH.

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

Uses
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 is_associated_with::gastrinoma, is_associated_with::pancreatitis or is_associated_with::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.

Osmoregulation
Secretin modulates water and is_associated_with::electrolyte transport in is_associated_with::pancreatic duct cells, liver is_associated_with::cholangiocytes, and is_associated_with::epididymis epithelial cells. It is found to play a role in the is_associated_with::vasopressin-independent regulation of renal water reabsorption.

Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the is_associated_with::hypothalamus and along the neurohypophysial tract to is_associated_with::neurohypophysis. During increased osmolality, it is released from the is_associated_with::posterior pituitary. In the hypothalamus, it activates is_associated_with::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 is_associated_with::syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of is_associated_with::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."

Food intake
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.