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Pathway Description
Roxatidine Acetate Action Pathway
Homo sapiens
Drug Action Pathway
Roxatidine acetate is an anti-ulcer agent, that works through antagonizing the histamine H2 receptor. It is used to reduce abdominal pain, heartburn, acid indigestion and acid reflux. The pathway begins in the stomach, where roxatidine acetate inhibits the histamine H2 receptor on the surface of the parietal cell. Now in the gastric endothelial cell, potassium-transporting ATPase units are inhibited by G-Protein signalling cascade through somatostatin receptor type 4, which is activated by somatostatin. At the same time, potassium-transporting ATPase is activated by the G-protein signalling cascade, through histamine H2 receptor which is inhibited by ranitidine, gastrin/cholecystokinin type B receptor, and muscarinic acetylcholine receptor M3 which are activated by histamine, gastrin and acetylcholine, respectively. The potassium transporting ATPase also converts water and ATP to a phosphate molecule and ADP. Alongside the transporters, potassium is brought into the cell. Carbonic anhydrase 1 uses water and carbon dioxide to create hydrogen carbonate and a hydrogen ion, which are both transported out of the endothelial cell, into the gastric lumen. A chloride ion is transported into the gastric endothelial cell through a chloride anion exchanger and is transported out of the cell through a chloride intracellular channel protein 2, back into the gastric lumen.
References
Roxatidine Acetate Pathway References
Nakamura H, Sano H, Yamazaki M, Sugiyama Y: Carrier-mediated active transport of histamine H2 receptor antagonists, cimetidine and nizatidine, into isolated rat hepatocytes: contribution of type I system. J Pharmacol Exp Ther. 1994 Jun;269(3):1220-7.
Pubmed: 7912279
Gastric Acid Production References
Wolfe MM, Soll AH: The physiology of gastric acid secretion. N Engl J Med. 1988 Dec 29;319(26):1707-15. doi: 10.1056/NEJM198812293192605.
Pubmed: 3060722
Schubert ML: Gastric acid secretion. Curr Opin Gastroenterol. 2016 Nov;32(6):452-460. doi: 10.1097/MOG.0000000000000308.
Pubmed: 27607343
Schubert ML: Functional anatomy and physiology of gastric secretion. Curr Opin Gastroenterol. 2015 Nov;31(6):479-85. doi: 10.1097/MOG.0000000000000213.
Pubmed: 26376477
Heitzmann D, Warth R: No potassium, no acid: K+ channels and gastric acid secretion. Physiology (Bethesda). 2007 Oct;22:335-41. doi: 10.1152/physiol.00016.2007.
Pubmed: 17928547
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