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Pathway Description
Rabeprazole Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Created: 2013-09-11
Last Updated: 2019-08-16
Rabeprazole is a drug that belongs to the anti secretory drug class. It is used as an anti-ulcer medication, and helps relieve gastric acid reflux, gastric irritation and gastric pain. It inhibits the proton pump action of ATPase, which blocks the final step of gastric acid secretion. The pathway begins in the parietal cell in the stomach, where rabeprazole and a hydrogen ion use the active metabolite in rabeprazole —rabeprazole thioether — to inhibit potassium-transporting ATPase at the secretory surface of the gastric parietal cell. Now in the gastric endothelial cell, these secretory surfaces are inhibited by rabeprazole and 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, 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
Rabeprazole Pathway References
DiPiro, J.T., Talbert, R.L., Yee, G.C., Matzke, G.R., Wells, B.G, & Posey, M.L. Pharmacotherapy: A pathologic approach. (6th ed) (2005) p.621-623. New York: McGraw-Hill Medical Publishing Division.
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Pubmed: 10963283
Pariet. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved July 1, 2009.
Ma JY, Song YH, Sjostrand SE, Rask L, Mardh S: cDNA cloning of the beta-subunit of the human gastric H,K-ATPase. Biochem Biophys Res Commun. 1991 Oct 15;180(1):39-45. doi: 10.1016/s0006-291x(05)81251-3.
Pubmed: 1656976
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Pubmed: 15057823
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Pubmed: 15489334
Maeda M, Oshiman K, Tamura S, Futai M: Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region. J Biol Chem. 1990 Jun 5;265(16):9027-32.
Pubmed: 2160952
Newman PR, Greeb J, Keeton TP, Reyes AA, Shull GE: Structure of the human gastric H,K-ATPase gene and comparison of the 5'-flanking sequences of the human and rat genes. DNA Cell Biol. 1990 Dec;9(10):749-62. doi: 10.1089/dna.1990.9.749.
Pubmed: 2176086
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Pubmed: 15057824
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