EFFECT OF COCAINE, PHENOXYBENZAMINE AND CALCIUM ON THE INHIBITION OF NOREPINEPHRINE OUTPUT FROM THE CAT SPLEEN BY GUANETHIDINE

¹ Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Guanethidine decreased the contraction of the nictitating membrane elicited by stimulation of preganglionic sympathetic nerves to the superior cervical ganglia. Cocaine (5 mg/kg) antagonized the inhibition produced by a low dose of guanethidine (2.5 mg/kg) by about 80% but was unable to antagonize that produced by high doses (10 mg/kg or more). In the perfused spleen of the cat, both norepinephrine output and the increase in peripheral resistance caused by sympathetic nerve stimulation or by injection of potassium were reduced by 90% by guanethidine (0.3 µg/ml) in 20 mm. In the presence of guanethidine, cocaine (10 µg/ml) only partially restored the norepinephrine output (20%) but almost fully restored the increase in peripheral resistance (60-100%). Prior perfusion with cocaine only slightly antagonized the inhibitory effect of guanethidine. In the presence of phenoxybenzamine (10 µg/ml), the inhibitory effect of guanethidine on norepinephnine output was initially blocked but did slowly become manifest on prolonged perfusion. In the presence of guanethidine, high calcium (50 mM) restored the norepinephrine output to 50% of the control level. Prior perfusion with high calcium inhibited the guanethidine-induced decrease in norepinephrme output.