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 potential targets for the
drug. We conclude that
ME-3407 is a promising
drug for treating
peptic ulcers, as well as a useful tool for studying mechanisms of parietal cell activation, especially related to the recruitment and recycling of the
proton pump.