Inhibitory mechanism of protamine on catecholamine sceretion

Protamine is clinically used to reverse the anticoagulant effects of heparin. But, in some cases, hypotension and shock are caused by intravenous administration of protamine. The inhibitory mechanisms of protamine on sympathetic nervous activity has not been well established. In the present study, we investigated the effects of protamine on serum norepinephrine level in rats, and on catecholamine secretion from cultured bovine adrenal medullary cells. In control rats, protamine ( 10 mg/kg, i.v.) lowered the arterial blood pressure and the serum level of norepinephrine. When rats were pretreated by heparin ( 1000 units/kg, i.v.), protamine did not lower the arterial blood pressure and the serum level of norepinephrine. In cultured bovine adrenal medullaly cells, protamine inhibited carbachol-and veratridine-evoked catecholamine secretion ^^45 Ca^2+ influx and ^^22 Na^+ influx in a concentration-dependent manner (10-100 μg/ml). 56 mM K^+ -induced secretion of catecholamine and ^^45 Ca^2+ influx were also inhibited by protamine. Heparin (3.5-14 U/ml) reversed the inhibitory effect of protamine ( 100 μg/ml) on catecholamine secretion. These results suggest that protamine shows the inhibitory effects on cardiovascular system by lowering the serum level of norepinephrine and that protamine inhibits catecholamine secretion from the to the adrenal medulla by interfering with Na^+ influx and Ca^2+ influx.