Molecular Pharmacology, Vol 10, 450-456, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

[³H]-Propranolol Binding Sites in Myocardial Membranes: Nonidentity with Beta Adrenergic Receptors

¹ Cardiology Division, Department of Medicine, and Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710

[³H]Propranolol binds rapidly and reversibly to sites in membranes prepared from canine ventricular myocardium. Two orders of sites were identified. The higher-order sites have a value (equilibrum constant) of 4.57 x 10⁴ M^-1 and a binding capacity of 3.2 x 10^-8 mole/ mg of protein. For the lower-order sites K = 4.32 x 10² M^-1 and binding capacity is 8.4 x 10^-7 mole/mg of protein. Nine adrenergic antagonist drugs were tested for their ability to block [³H]propranolol binding and block isoproterenol activation of adenylate cyclase in dog heart membranes. No clear correlation between the two functions was found. d- and l-Propranolol competed with equal effectiveness for the propranolol binding sites, but l-propranolol was 50 times more potent than the d isomer in blocking cyclase activation. The beta adrenergic blocking agent dichloroisoproterenol was a very weak inhibitor of [³H]-propranolol binding. Chlorpromazine and haloperidol inhibited both propranolol binding and cyclase activation. It is concluded that the [³H]propranolol binding sites studied here are unrelated to the myocardial beta adrenergic receptors and may be involved in mediating the more general membrane or local anesthetic effects of propranolol. Beta adrenergic receptor binding sites presumably represent too small a fraction of myocardial membrane sites capable of binding propranolol to be revealed by binding studies of this type.

Note:
ACKNOWLEDGMENT The authors are indebted to Dr. Edgar Harber, Massachusetts General Hospital, in whose laboratory part of these studies were performed.