title: Proton-Potassium (H(+)/K(+)) ATPases: Properties and Roles in Health and Diseases.
abstract: As a physiological phenomenon, acid secretion from the stomach was known already at least in the 17th century. But its mechanism was elucidated in more recent times only. At the end of the 20th century, gastric H(+)/K(+)-ATPase in the parietal cells was found to be responsible for a final step of H(+) secretion in these cells. In this century, several Cl(-)-transporting proteins for gastric acid (hydrochloric acid; HCl) secretion have been found. As inhibitors of gastric acid secretion, histamine H2 receptor antagonists (H2 blockers) were developed in the 1970's. This discovery brought a great benefit; that is, peptic ulcers became treatable by administration of a drug. In 1980's, proton pump inhibitors (PPIs) were developed. The target of PPIs is gastric H(+)/K(+)-ATPase and the PPIs exert generally more potent effects compared with H2 blockers. Most recently, several K(+)-competitive inhibitors of the ATPase are being developed. Here, we introduce gastric H(+)/K(+)-ATPase and its related proteins for gastric acid secretion, and several gastric diseases and their treatment by medicines.
authors: Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama City, Toyama, 930-0194, Japan. sakaih@pha.u-toyama.ac.jp.
authors: Hideki
authors: H
authors: Sakai
authors: Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama City, Toyama, 930-0194, Japan.
authors: Takuto
authors: T
authors: Fujii
authors: Takeguchi Digestive Research, Toyama, 930-0125, Japan. qqze72p9@tiara.ocn.ne.jp.
authors: Noriaki
authors: N
authors: Takeguchi
mesh_terms: D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013270:Stomach / Q000201:enzymology
chemical_list: D054328:Proton Pump Inhibitors; D017506:H(+)-K(+)-Exchanging ATPase
keywords: Cl− transporter; Gastric acid; K+ channel; PPI; Parietal cell; Proton pump; Stomach