Inhibition of adenylate cyclase by arsenite and cadmium: evidence for a vicinal dithiol requirement.
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 -7mM produced only 60% inhibition. Its effect, however, was greatly potentiated by equimolar 2,3 dimercaprol- wherein 0.7 mM sodium arsenite inhibited 100% with an apparent Ki of 0.1 mM. Equimolar mercaptoethanol was less effective in potentiating sodium arsenite inhibition. Thus 0.7mM sodium arsenite in the presence of equimolar mercaptoethanol inhibited adenylate cyclase 56%. Excess 2,3 dimercaprol reversed inhibition by sodium 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%. These results suggest that turkey erythrocyte membranes contain closely juxtaposed thiol groups and that interaction of such groups with arsenate interferes with the catalytic function of adenulate cyclase.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood; D000494:Allosteric Regulation; D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D001665:Binding Sites; D002104:Cadmium / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000201:enzymology; D005459:Fluorides / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014422:Turkeys
D000067956:Adenylyl Cyclase Inhibitors; D006150:Guanine Nucleotides; D013438:Sulfhydryl Compounds; D002104:Cadmium; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D001151:Arsenic; D005459:Fluorides