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The novel acid pump antagonists for anti-secretory actions with their peculiar applications beyond acid suppression.

Authors
Yeo, M; Kwak, MS; Kim, DK; Chung, IS; Moon, BS; Song, KS; Hahm, KB
Citation
Journal of clinical biochemistry and nutrition, 38(1):1-8, 2006
Journal Title
Journal of clinical biochemistry and nutrition
ISSN
0912-00091880-5086
Abstract
The H+/K+-ATPase of gastric parietal cell exchanges luminal K+ for cytoplasmic H+, of which outcome is gastric acidification with outflux of hydronium ion (H3O+). Secretion of gastric acid from the H+/K+-ATPase is stimulated by neuronal sensing and elaborately regulated various neuronal transmitters and hormones, consequently resulting in anchoring of the H +/K+-ATPase in canaliculi membrane of gastric parietal cell. Since hypersecretion of gastric acid or a defect of its barrier function is considered as a principal casual factor in the acid-related diseases such as duodenal and gastric ulcer, reflux esophagitis, and some types of gastritis, the development of anti-secretory agents including PPIs (proton pump inhibitors) and H2-RAs (histamine type 2 receptor antagonists) has revolutionized during the second millennium. Similar considerations applying to design of compounds substituting K+ led to the development of acid pump antagonists (APAs), of which advantages are independent of secretory status, no lag time required, reversible in actions allowing "on-demand dosage". Our recent studies revealed that these inhibitors of H+/K +-ATPase could be extensively applied for the selective induction of cancer cell apoptosis, a significant anti-inflammatory and gastroprotective action far beyond acid suppression. In the current review, we described the mechanistic regulation of gastric acid secretion with pump inhibitor, the difference and characteristics between PPI and APA based on the molecular mechanism, and their new applications beyond acid suppression.
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
Journal Papers > Research Organization > Genomic Research Center for Gastroenterology
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