INHIBITION OF ADENYLATE-CYCLASE BY ARSENITE AND CADMIUM - EVIDENCE FOR A VICINAL DITHIOL REQUIREMENT

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 2  (6) , 393-404
Abstract
The effect of sodium arsenite and cadmium chloride on adenylate cyclase activity was examined in turkey erythrocyte membranes. Sodium arsenite was a weak inhibitor of adenylate cyclase 7 mM produced only 60% inhibition. Its effect was greatly potentiated by equimolar 2,3 dimercaprol wherein 0.7 mM sodium arsenite inhibited 100% with an apparent Ki [inhibition constant] of 0.1 mM. Equimolar mercaptoethanol was less effective in potentiating sodium arsenite inhibition. Thus 0.7 mM sodium arsenite in the presence of equimolar mercaptoethanol inhibited adenylate cyclase 56%. Excess 2,3 dimercaprol reversed inhibition of Na arsenite or cadmium chloride. Sodium arsenite or cadmium chloride inhibited all forms of adenylate cyclase activity tested, including nonhormonal stimulation. Equimolar sodium arsenite and dimercaprol, at concentrations that caused 100% inhibition of adenylate cyclase activity, reduced the binding of the .beta.-receptor specific ligand iodohydroxybenzylpindolol by less than 15%. Turkey erythrocyte membranes may contain closely juxtaposed thiol groups whose interaction with arsenite interferes with the catalytic function of adenylate cyclase.