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 language | English |
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Pages (from-to) | 51-54 |
Number of pages | 4 |
Journal | Arzneimittel-Forschung/Drug Research |
Volume | 44 |
Issue number | 1 |
State | Published - 1994 |
Keywords
- CAS 60940-34-3
- H,K-ATPase, inhibition
- ebselen pharmacology
ASJC Scopus subject areas
- Drug Discovery