Restoration of Norepinephrine Responsiveness of Solubilized Myocardial Adenylate Cyclase by Phosphatidylinositol

Gerald S Levey

doi:10.1016/s0021-9258(19)45900-0

Abstract

Abstract We have recently described the preparation of a solubilized cat myocardial adenylate cyclase which is unresponsive to norepinephrine, glucagon, histamine, and thyroxine, the hormones which activate the membrane-bound adenylate cyclase. The addition of phosphatidylinositol totally restored the norepinephrine activation of the solubilized adenylate cyclase, whereas, phosphatidylserine and phosphatidylethanolamine did not. Half-maximal activation was achieved with norepinephrine, 8 x 10-8 m, a concentration approximately 1% of that required in particulate preparations. Norepinephrine activation of adenylate cyclase in the presence of phosphatidylinositol was abolished by the beta adrenergic blocking agent, dl-propranolol.

Highlights

Norepinephrine activation of adenylate cyclase in the presence of phosphatidylinositol was abolished by the beta adrenergic blocking agent, DL-propranolol
The membrane-bound cat myocardial adenylate cyclase is activated by several hormones including catecholamines (l), glucagon [2, 3], histamine [4], and thyroxine and triiodothyronine [5]
Addition of phosphatidyleerine totally restored its responsiveness to glucagon [11] and histamine,l but not to norepinephrine

Summary

Responsive Adenylate

We have recently described the preparation of a solubilized cat myocardial adenylate cyclase which is unresponsive to norepinephrine, glucagon, histamine, and thyroxine, the hormones which activate the membrane-bound adenylate cyclase. The addition of phosphatidylinositol totally restored the norepinephrine activation of the solubilized adenylate cyclase, whereas, phosphatidylserine and phosphatidylethanolamine did not. Norepinephrine activation of adenylate cyclase in the presence of phosphatidylinositol was abolished by the beta adrenergic blocking agent, DL-propranolol. We wish to report that another lipid, phosphatidylinositol, restores the norepinephrine responsiveness of mycoardial adenylate cyclase and that the activation of the enzyme is abolished by the beta adrenergic blocking agent, DL-propranolol. The norepinephrine-mediated activation of the particulate myocardial adenylate cyclase is abolished by beta adrenergic blocking agents including m-propranolol [1, 3]. Phosphatidylinositol restored the norepinephrine responsiveness of the solubilized enzyme over the concentration range 0.025 pg per incubation to 0.25 fig per incubation (0.4 pg per ml to 4.0 pg per ml).

TABLE I

Solubilized enzyme

Findings

Hen Oviduct Ribonucleic