Inhibition by Chlorpromazine, Metals and I-Ascorbic Acid of Calcium-ATPase and Magnesium-ATPase in Bovine Adrenal Medullary Microsomes

Abstract

Effects of chlorpromazine, metals and I-ascorbic acid (AA) on Ca²⁺-ATPase and Mg²⁺-ATPase in microsomal and granular fractions obtained from the bovine adrenal medulla were studied. Marker enzyme analysis on microsomal subfractions in a discontinuous sucrose density gradient showed a correlation of distribution between ATPase activities and plasma membrane. The two ATPase activities in such plasma membrane-rich microsomes were reduced by chlorpromazine, Hg²⁺ and Cu²⁺ (0.3 mM of each), and their effects were greater on the Mg²⁺-ATPase activity. Zn²⁺(0.3 mM) also reduced only the Mg²⁺-ATPase activity. AA (3 mM) reduced the two ATPase activities to an equal extent. Nevertheless, the inhibitions of ATPases by Hg²⁺, Cu²⁺ and Zn²⁺ were decreased, unaltered and additively enhanced in combination with AA, respectively. We also observed high Mg²⁺-ATPase activity in the granule-rich fraction, but this ATPase activity was unaffected by all of the above agents. These results indicate that Mg²⁺-ATPase in the plasma membrane-rich microsome of adrenal medulla is inhibited by chlorpromazine, Hg²⁺, Cu²⁺ and Zn²⁺ more significantly than Ca²⁺-ATPase, but Mg²⁺-ATPase in the granular fraction is unaffected, and that AA changes the potency of inhibition by some metals of ATPases diversely.