Ecabet sodium, a locally acting antiulcer drug, inhibits urease activity of Helicobacter pylori.
In order to clarify the mechanism of the anti-Helicobacter pylori action of ecabet sodium (ecabet), a locally acting antiulcer drug, we evaluated the effects of ecabet on H. pylori urease activity in vitro. H. pylori was cultured and a crude preparation of urease was made. Urea-dependent survival of H. pylori at acid pH was significantly inhibited by ecabet. The urease activity of intact cells and a crude enzyme preparation from H. pylori had two pH optima: pH 4.5-5.0 and 8.0. Ecabet (1-4 mg/ml) concentration dependently inhibited the urease activity of both preparations at pH 5.0, but there was no inhibition at pH 8.0. The enzyme activity was inhibited by ecabet gradually and was not restored by dilution, in contrast to the inhibition elicited by benzohydroxamic acid, a specific and reversible urease inhibitor. These results suggest that irreversible inhibition of H. pylori urease activity contributes to the anti-H. pylori action of ecabet.
Ito
Y
Y
Lead Optimization Research Laboratory, Tanabe Seiyaku, Toda, Saitama, Japan. yutaka-i@tanabe.co.jp
Shibata
K
K
Hongo
A
A
Kinoshita
M
M
D045784:Abietanes; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D014510:Urease / Q000037:antagonists & inhibitors*
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; C061681:ecabet; D014510:Urease