Mechanism of the inhibition of hog gastric H+,K+-ATPase by the seleno-organic compound ebselen

Y. Tabuchi*, T. Ogasawara, K. Furuhama

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The effect of 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen, CAS 60940-34-3), a seleno-organic compound, on the partial reaction steps of H+,K+-ATPase in hog leaky gastric vesicles was examined. Ebselen inhibited K+-dependent ATPase activity (IC50 = 0.06 μmol/l), phosphoenzyme formation (IC50 = 0.25 μmol/l), and K+-dependent p-nitrophenylphosphatase activity (IC50 = 0.09 μmol/l: dephosphorylation step of this enzyme). Furthermore, this compound prevented changes in the fluorescence intensity of fluorescein isothiocyanate-labeled enzyme (E1 → E2K form, IC50 = 0.33 μmol/l). Pretreatment with 2 mmol/l of dithiothreitol (DTT) used as a sulfhydryl compound completely protected against these inhibitory effects. These findings indicate that ebselen-induced inactivation of gastric H+,K+-ATPase may result from prevention of the partial reaction steps, which include phosphorylation, dephosphorylation and conformational change (E1 → E2K form), through interference with sulfhydryl groups of the enzyme.

Original languageEnglish
Pages (from-to)51-54
Number of pages4
JournalArzneimittel-Forschung/Drug Research
Volume44
Issue number1
StatePublished - 1994

Keywords

  • CAS 60940-34-3
  • H,K-ATPase, inhibition
  • ebselen pharmacology

ASJC Scopus subject areas

  • Drug Discovery

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