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Inhibition of partially purified K/H + ‐ATPase from guinea‐pig isolated and enriched parietal cells by substituted benzimidazoles
Author(s) -
Beil W.,
Sewing K.Fr.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10803.x
Subject(s) - parietal cell , h(+) k(+) exchanging atpase , atpase , differential centrifugation , guinea pig , enzyme , biochemistry , chemistry , verapamil , gastric mucosa , biology , microbiology and biotechnology , calcium , stomach , endocrinology , organic chemistry
1 The cellular and subcellular distributions of adenosinetriphosphatases (ATPases) were examined in guinea‐pig gastric mucosal cells. All cell types displayed Mg 2+ ‐ATPase and bicarbonate (HCO &3bar; )‐stimulated ATPase activity. K + ‐ATPase was located only in fractions derived from parietal cells. 2 Differential and density‐gradient centrifugation of material prepared from parietal cells revealed that K + ‐ATPase activity was located in a tubulo‐vesicular membrane fraction. Enzyme activity was ten fold greater in this fraction than in a crude parietal cell homogenate. 3 The substituted benzimidazoles, omeprazole and picoprazole, inhibited K + ‐ATPase (IC 50 1.8 ± 0.5 μmol 1 −1 and 3.1 ± 0.4 μmol 1 −1 , respectively). Detailed kinetic analysis indicated that these compounds were non‐competitive and reversible inhibitors of the enzyme. In contrast cimetidine and verapamil were without effect on the enzyme. 4 The relevance of the inhibition of K + ‐ATPase to the antisecretory activity of the benzimidazoles, in experimental animals and man, is discussed.