H] Propranolol binding sites in myocardial membranes: nonidentity with beta adrenergic receptors
[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 (equilibrium 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.