Preferential uncoupling by manganese of alpha adrenergic receptor mediated inhibition of adenylate cyclase in human platelets

Mn ++ was found to preferentially uncouple the alpha receptor mediated inhibition of adenylate cyclase in human platelets under conditions where PGE 1 stimulation of the enzyme was preserved. Since epinephrine competition curves with the antagonist radioligand [ 3H]yohimbine were unchanged by Mn ++, it is likely that the Mn ++ perturbs the interaction of an inhibitory regulatory component with adenylate cyclase rather than with the alpha receptor. The ability of low concentrations of Mn ++ to selectively uncouple a functionally distinct pathway which mediates inhibition of adenylate cyclase by alpha-adrenergic agonists and guanine nucleotides should provide a useful tool for probing the mechanisms of hormonal regulation of the enzyme's activity.