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Pathway Description
Ranitidine H2 Anti-Histamine Action Pathway
Homo sapiens
Drug Action Pathway
Ranitidine is an histamine H2 receptor antagonist used to treat stomach ulcers and Gastroesophageal Reflux Disease (GERD). After being taken orally, it is absorbed in the GI tract and travels through the blood to get to the stomach epithelium. Ranitidine binds reversibly to the histamine H2 receptor blocking histamine from binding instead. This blocks the downstream Gs cascade which produces cyclic adenosine monophosphate (cAMP) which is an activator for the potassium-hydrogen ATPase pump (H+/K+ ATPase pump). The pump is responsible for secreting hydrogen ions into the stomach lumen increasing the acidity of the stomach environment. By blocking adenylate cyclase signalling pathway from the histamine H2 receptor less hydrogen ions are secreted into the stomach lumen increasing the pH. The less acidic environment doesn't irritate the stomach as much. The H+/K+ ATPase pump can still be activated through gastrin and acetylcholine through the phospholipase C signalling pathway, but blocking the adenylate cyclase pathway helps reduce the acidity.
References
Ranitidine H2 Anti-Histamine Pathway References
Washabau R. J. Chapter 1 - Integration of Gastrointestinal Function. Canine and Feline Gastroenterology 1-31, 2013.
Habibi A, Riley T, E. Chapter 25 - Antihistamines: H1- and H2-Blockers. Complications in Anesthesia (Second Edition) 92-93, 2007.
Prinz C, Zanner R, Gerhard M, Mahr S, Neumayer N, Hohne-Zell B, Gratzl M: The mechanism of histamine secretion from gastric enterochromaffin-like cells. Am J Physiol. 1999 Nov;277(5):C845-55. doi: 10.1152/ajpcell.1999.277.5.C845.
Pubmed: 10564076
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Engevik AC, Kaji I, Goldenring JR: The Physiology of the Gastric Parietal Cell. Physiol Rev. 2020 Apr 1;100(2):573-602. doi: 10.1152/physrev.00016.2019. Epub 2019 Oct 31.
Pubmed: 31670611
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