Restoration of glucagon responsiveness of solubilized myocardial adenyl cyclase by phosphatidylserine

Abstract

Solubilized preparations of cat myocardial adenyl cyclase have been previously shown to be unresponsive to glucagon, norepinephrine, and thyroxine, hormones which activate the particulate adenyl cyclase. This report demonstrates that the addition of phosphatidyl-serine to a solubilized preparation freed of detergent, completely restores the glucagon responsiveness of adenyl cyclase. Half-maximal activity and maximal percent increase in cyclic 3′,5′-AMP accumulation were virtually identical to that previously reported for the particulate preparation. Norepinephrine activates myocardial adenyl cyclase by a receptor mechanism separate and distinct from the glucagon receptor and in contrast to glucagon, norepinephrine responsiveness was not restored by phosphatidylserine. Phosphatidylserine may produce a configurational change in the adenyl cyclase which then allows glucagon binding and activation of adenyl cyclase.