title: [Inhibitory action of E3810 on H+,K(+)-ATPase and gastric acid secretion in vitro].
abstract: The inhibitory action of (+-)-sodium 2-[(4-(3-methoxypropoxy)-3-methylpyridine-2-yl) methylsulfinyl]-1H- benzimidazole (E3810) on H+,K(+)-ATPase and gastric acid secretion in vitro was investigated, and it was compared with those of omeprazole (OPZ). E3810 concentration-dependently inhibited the H+,K(+)-ATPase activity of hog gastric vesicles. Its IC50 was 0.26 microM at pH 6.1. The inhibition was irreversible in nature and reversed by dithiothreitol. The potency of E3810 was 10-times that of omeprazole. Acidification of the intravesicular (luminal) space increased 1000-fold the potency of E3810, indicating that E3810 is a specific inhibitor which binds to the luminal cysteine residue of H+,K(+)-ATPase. Prolonged incubation of up to 180 min in the absence of thiol reagents of rabbit gastric glands which had been inhibited by a low concentration of E3810 (0.3 and 0.5 microM) time-dependently and completely reversed the inhibition, as determined by aminopyrine uptake, whereas it did not recover the acid secretion in omeprazole-treated glands. These results suggest that the acid-activated E3810 is a potent specific inhibitor of H+,K(+)-ATPase, and that the duration of the inhibitory action of E3810 is much shorter than that of omeprazole in isolated gastric glands.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co. Ltd., Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujisaki
authors.forename: K
authors.initials: K
authors.lastname: Oketani
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: I
authors.initials: I
authors.lastname: Yamatsu
authors.forename: N
authors.initials: N
authors.lastname: Takeguchi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D011817:Rabbits; D064750:Rabeprazole; D013552:Swine
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D009853:Omeprazole