Secretin
Ensembl |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt |
| ||||||||
| RefSeq (mRNA) |
| ||||||||
| RefSeq (protein) |
| ||||||||
| Location (UCSC) | Chr 11: 0.63 – 0.63 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
| View/Edit Human | |||
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.[3] In humans, the secretin peptide is encoded by the SCT gene.[4]
Secretin helps regulate the
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.[8]
In 2007, secretin was discovered to play a role in
History
In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion.[11] 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. This type of 'chemical messenger' substance is now called a hormone, a term coined by Starling in 1905.[12]
Secretin is frequently erroneously stated to have been the first hormone identified.[13] 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.[14][15]
Structure
Secretin is initially synthesized as a 120 amino acid precursor protein known as
The mature secretin peptide is a linear
Secretin also has an amidated
Physiology
Production and secretion
Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the
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
Secretin release is inhibited by
Function
pH regulation
Secretin primarily functions to neutralize the pH in the
Secretin targets the
Secretin also increases water and bicarbonate secretion from duodenal
It counteracts
Osmoregulation
Secretin modulates
Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the
It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D
Food intake
Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the
Uses
Secretin is used in a diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with magnetic resonance imaging, a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum.[34][35][36]
A recombinant human secretin has been available since 2004 for these diagnostic purposes.[37] There were problems with the availability of this agent from 2012 to 2015.[38]
Research
A wave of enthusiasm for secretin as a possible treatment for autism arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest.[39][40][41]
A high-affinity and optimized secretin receptor antagonist (Y10,c[E16,K20],I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation.[42]
See also
References
- ^ a b c ENSG00000274473 GRCh38: Ensembl release 89: ENSG00000070031, ENSG00000274473 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7000396.
- ^ PMID 2315322.
- S2CID 12850155.
- OCLC 62326921.
- PMID 30850822.
- PMID 2395872.
- ^ PMID 17283064.
- ^ PMID 19805236.
- PMID 16992627.
- PMID 15308687.
- .
- PMID 16992252.
- PMID 16992252.
- ISBN 978-0-7216-9398-9.
- ^ ISBN 978-0-7216-2888-2.
- PMID 4945081.
- ^ ISBN 978-0-07-022001-0.
- ISBN 978-0-07-140236-1.[page needed]
- S2CID 7039025.
- ^ ISBN 978-0-7216-0240-0.
- ^ Gardner JD (1978). "Receptors and gastrointestinal hormones". In Sleisenger MH, Fordtran JS (eds.). Gastrointestinal Disease (2nd ed.). Philadelphia: WB Saunders Company. pp. 179–95.
- PMID 631638.
- ISBN 978-0-7020-3085-7.
- ISBN 978-1-4377-1753-2.
- PMID 5415678.
- PMID 7875488.
- PMID 9148905.
- S2CID 1189550.
- PMID 19318428.
- PMID 20739612.
- PMID 20927047.
- PMID 18506918.
- PMID 20510825.
- ^ "Secretin stimulation test". MedlinePlus Medical Encyclopedia. United States National Library of Medicine. Retrieved 2008-11-01.
- ^ "Human Secretin". Patient Information Sheets. United States Food and Drug Administration. 2004-07-13. Archived from the original on May 11, 2009. Retrieved 2008-11-01.
- ^ American Society of Health-System Pharmacists (5 August 2015). "Secretin Injection". Current Drug Shortage Bulletin. Archived from the original on 9 November 2016. Retrieved 9 November 2016.
- ^ Stokstad E (18 July 2008). "News this Week: Stalled Trial for Autism Highlights Dilemma of Alternative Treatments". Science. p. 324.
- ^ "The Use of Secretin to Treat Autism". NIH News Alert. United States National Institutes of Health. 1998-10-16. Retrieved 2008-11-30.
- PMID 10588965.
- PMID 32217097.
Further reading
- Saus E, Brunet A, Armengol L, Alonso P, Crespo JM, Fernández-Aranda F, et al. (October 2010). "Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients". Journal of Psychiatric Research. 44 (14): 971–978. PMID 20398908.[permanent dead link]
- Bertenshaw GP, Turk BE, Hubbard SJ, Matters GL, Bylander JE, Crisman JM, et al. (April 2001). "Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity". The Journal of Biological Chemistry. 276 (16): 13248–13255. PMID 11278902.
- Lee LT, Lam IP, Chow BK (November 2008). "A functional variable number of tandem repeats is located at the 5' flanking region of the human secretin gene plays a downregulatory role in expression". Journal of Molecular Neuroscience. 36 (1–3): 125–131. S2CID 29982279.
- Nussdorfer GG, Bahçelioglu M, Neri G, Malendowicz LK (February 2000). "Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis". Peptides. 21 (2): 309–324. S2CID 42207065.
- Lossi L, Bottarelli L, Candusso ME, Leiter AB, Rindi G, Merighi A (December 2004). "Transient expression of secretin in serotoninergic neurons of mouse brain during development". The European Journal of Neuroscience. 20 (12): 3259–3269. S2CID 398304.
- Lee SM, Yung WH, Chen L, Chow BK (February 2005). "Expression and spatial distribution of secretin and secretin receptor in human cerebellum". NeuroReport. 16 (3): 219–222. S2CID 10500720.
- Lam IP, Lee LT, Choi HS, Alpini G, Chow BK (July 2009). "Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP)". American Journal of Physiology. Gastrointestinal and Liver Physiology. 297 (1): G90–G97. PMID 19372104.
- Yamagata T, Aradhya S, Mori M, Inoue K, Momoi MY, Nelson DL (August 2002). "The human secretin gene: fine structure in 11p15.5 and sequence variation in patients with autism". Genomics. 80 (2): 185–194. PMID 12160732.
- Lee LT, Tan-Un KC, Chow BK (July 2006). "Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by cyclin-dependent kinase 1". Annals of the New York Academy of Sciences. 1070 (1): 393–398. S2CID 36959997.
- Onori P, Wise C, Gaudio E, Franchitto A, Francis H, Carpino G, et al. (July 2010). "Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP-dependent signaling mechanisms of secretin receptor". International Journal of Cancer. 127 (1): 43–54. S2CID 2789418.
- Lee LT, Tan-Un KC, Pang RT, Lam DT, Chow BK (July 2004). "Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element". Molecular Endocrinology. 18 (7): 1740–1755. PMID 15118068.
- Lu Y, Owyang C (July 2009). "Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways". Neurogastroenterology and Motility. 21 (7): 754–e47. PMID 19239625.
- Gandhi S, Rubinstein I, Tsueshita T, Onyuksel H (January 2002). "Secretin self-assembles and interacts spontaneously with phospholipids in vitro". Peptides. 23 (1): 201–204. S2CID 19705403.
- Lam IP, Lee LT, Choi HS, Chow BK (July 2006). "Localization of small heterodimer partner (SHP) and secretin in mouse duodenal cells". Annals of the New York Academy of Sciences. 1070 (1): 371–375. S2CID 37244976.
- Luttrell LM (July 2008). "Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors". Molecular Biotechnology. 39 (3): 239–264. S2CID 45173229.
- Du K, Couvineau A, Rouyer-Fessard C, Nicole P, Laburthe M (October 2002). "Human VPAC1 receptor selectivity filter. Identification of a critical domain for restricting secretin binding". The Journal of Biological Chemistry. 277 (40): 37016–37022. PMID 12133828.
- Portela-Gomes GM, Johansson H, Olding L, Grimelius L (November 1999). "Co-localization of neuroendocrine hormones in the human fetal pancreas". European Journal of Endocrinology. 141 (5): 526–533. PMID 10576771.
- Mutoh H, Ratineau C, Ray S, Leiter AB (April 2000). "Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells". Alimentary Pharmacology & Therapeutics. 14 (Suppl 1): 170–175. S2CID 25989697.
External links
- Overview at colostate.edu
- Secretin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Nosek TM. "Section 6/6ch2/s6ch2_17". Essentials of Human Physiology. Archived from the original on 2016-03-24.