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Pathway Description
Ranitidine Action Pathway
Homo sapiens
Drug Action Pathway
Ranitidine 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 ranitidine 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
Ranitidine Pathway References
Bertaccini G, Coruzzi G: Control of gastric acid secretion by histamine H2 receptor antagonists and anticholinergics. Pharmacol Res. 1989 Jul-Aug;21(4):339-52.
Pubmed: 2570417
Pounder RE: Histamine H2-receptor antagonists and gastric acid secretion. Pharmacol Ther. 1984;26(2):221-34.
Pubmed: 6152495
Shamburek RD, Schubert ML: Pharmacology of gastric acid inhibition. Baillieres Clin Gastroenterol. 1993 Mar;7(1):23-54.
Pubmed: 8097411
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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