Solubilized myocardial adenylate cyclase. Restoration of histamine responsiveness by phosphatidylserine.
We have recently described the preparation of a solubilized cat myocardial adenylate cyclase which is unresponsive to histamine, norepinephrine, glucagon, and thyroxine, the hormones which activate the particulate enzyme. Since hormone receptors may consist of proteins and phospholipids, we determined the effect of several phospholipids on restoring the responsiveness of the solubilized adenylate cyclase to histamine. The addition of phosphatidylserine completely restored the histamine-mediated activation of the solubilized enzyme in contrast to phosphatidylethanolamine and phosphatidylinositol which were without effect. The concentration of histamine producing half-maximal activation of adenylate cyclase, 2 x 10(-5) M, was virtually identical with that observed in the particulate preparation. The antihistamine, diphenhydramine, 8 x 10(-5) M, abolished activation of adenylate cyclase by histamine in both the solubilized and particulate preparations. Phosphatidylserine also restored glucagon responsiveness, but did not restore norepinephrine responsiveness. It would appear that phosphatidylserine produced the necessary molecular configuration of the adenylate cyclase for histamine binding and activation of the enzyme.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002415:Cats; D000242:Cyclic AMP / Q000096:biosynthesis; D004155:Diphenhydramine / Q000494:pharmacology; D004789:Enzyme Activation; D005934:Glucagon / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000201:enzymology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D012995:Solubility
D010714:Phosphatidylethanolamines; D006632:Histamine; D004155:Diphenhydramine; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases