Molecular Pharmacology, Vol 20, 118-123, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Platelet Serotonin Transport by Propranolol

¹ Departments of Pharmacology and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, and Veterans Administration Medical Center, West Haven, Connecticut 06516

Transport of serotonin into human platelets is inhibited by the beta-adrenergic blocking agent, propranolol. Both D- and DL-propranolol, at a concentration of 1 µM, inhibit the initial rate of serotonin transport by approximately 50%, but do not affect the steady-state level of accumulation. Although most of the serotonin accumulated by intact platelets is stored in intracellular dense granules, this reserpine-sensitive component of platelet serotonin transport is not inhibited by propranolol. In isolated porcine platelet plasma membrane vesicles, DL-propranolol is a competitive inhibitor of serotonin transport with a K_I of 1.03 ± 0.27 µM. Moreover, propranolol displaces imipramine bound to the plasma membrane serotonin transporter. In contrast, propranolol does not inhibit transport of serotonin into membrane vesicles derived from platelet dense granules. These results indicate that propranolol inhibits platelet serotonin transport at the level of the plasma membrane.