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Secretin 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 ductal cells of the pancreas. It also stimulates the secretion of bicarbonate and water by in the bile duct, protecting it from bile acids by controlling the pH and promoting the flow in the duct. Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, cholecystokinin (CCK), stimulates the gallbladder to contract, delivering its stored bile.
Prosecretin is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by gastric acid. This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid.
In 2007, secretin was discovered to play a role in osmoregulation by acting on the hypothalamus, pituitary, and kidney.
Secretin is frequently erroneously stated to have been the first hormone identified. However, British researchers George Oliver and Edward Albert Schäfer had already published their findings of an adrenal extract increasing blood pressure and heart rate in brief reports in 1894 and a full publication in 1895, making adrenaline the first discovered hormone.
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–Histidine-Serine-Aspartic acid-Glycine-Threonine-Phenylalanine-Threonine-Serine-Glutamic acid-Leucine-Serine-Arginine-Leucine-Arginine-Aspartic acid-Serine-Alanine-Arginine-Leucine-Glutamine-Arginine-Leucine-Leucine-Glutamine-Glycine-Leucine-Valine–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; the acidity is due to hydrochloric acid in the chyme that enters the duodenum from the stomach via the pyloric sphincter. (2025). 9780070220010, McGraw-Hill, Medical Pub. Div. ISBN 9780070220010 Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine. (2025). 9780071402361, McGraw-Hill, Medical Pub. Div. ISBN 9780071402361
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 targets the pancreas; 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 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.
Secretin also increases water and bicarbonate secretion from duodenal Brunner's glands to buffer the incoming protons of the acidic chyme, (2025). 9780721602400, Elsevier Saunders. ISBN 9780721602400 and also reduces acid secretion by parietal cells of the stomach. (2025). 9780702030857, Churchill Livingstone. ISBN 9780702030857 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. (2025). 9781437717532, Saunders. ISBN 9781437717532
It counteracts blood glucose concentration spikes by triggering increased insulin release from pancreas, following oral glucose intake.
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."
A recombinant human secretin has been available since 2004 for these diagnostic purposes. There were problems with the availability of this agent from 2012 to 2015.
A high-affinity and optimized secretin receptor antagonist (Y10,cE16,K20,I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.
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