ME-3407, a new antiulcer agent, inhibits acid secretion by interfering with redistribution of H(+)-K(+)-ATPase

The American Journal of Physiology
T UrushidaniJ G Forte

Abstract

ME-3407 is a newly developed antiulcer drug that markedly promoted the healing of acetic acid-induced chronic ulcers in rats presumably due to potent inhibition of acid secretion. ME-3407 and its metabolites, the sulfoxide of which was preserved, produced dosedependent inhibition of aminopyrine accumulation by rabbit gastric glands stimulated by any agonist, suggesting that the site of their action was downstream from the production of second messengers. Although one of the metabolites, EF-4025, showed some inhibitory effects on functional activities of H(+)-K(+)-ATPase, ME-3407 itself was not a proton pump inhibitor. ME-3407, but not omeprazole, inhibited the stimulation-associated redistribution of H(+)-K(+)-ATPase from microsomes into the apical membranes in addition to delocalizing ezrin, a putative F-actin-membrane linker, from apical plasma membrane. ME-3407 and EF-4025 inhibited myosin light chain kinase (MLCK) and protein kinase A activities. Because another MLCK inhibitor, wortmannin, showed the same properties as ME-3407, i.e., inhibition of aminopyrine accumulation, inhibition of stimulation-associated redistribution of H(+)-K(+)-ATPase, and abnormal distribution of ezrin, we hypothesize that MLCK is one of the poten...Continue Reading

Citations

Nov 26, 1998·Japanese Journal of Pharmacology·K AkagiT Urushidani
Dec 26, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·David A AmmarXuebiao Yao
Dec 26, 2002·Annual Review of Physiology·Xuebiao Yao, John G Forte
Dec 21, 2000·American Journal of Physiology. Cell Physiology·Y MutoT Urushidani
Jun 16, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·S E MettlerJ G Forte

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