Interaction of Protamine with alpha- and beta-Adrenoceptor Stimulations inRat Myocardium

Background: Protamine alters the inotropic responses to beta -adrenoceptor stimulation, but its mechanism of action is not well-understood. Moreover, its interaction with alpha -adrenoceptor stimulation and the lusitropic (re laxation) response to beta -adrenoceptor stimulation remain unknown. Methods: The effects of protamine (10 or 100 mug/ml) on the responses induc ed by phenylephrine and isoproterenol were studied In rat left ventricular papillary muscles. Inotropic and lusitropic effects were studied under low and high loads. The authors also studied the interaction of protamine with forskolin (50 mum) and dibutyryl 3',5'-cAMP (0.5 mm). Data are mean percent age of baseline active force +/- SD. Results: In control groups, phenylephrine (135 +/- 17%, P < 0.05) and isopr oterenol (185 +/- 44%, P < 0.05) induced a positive inotropic effect. Isopr oterenol induced positive lusitropic effects under low and high loads. Prot amine abolished the inotropic responses to alpha- (102 +/- 23%, not signifi cant) and beta -adrenoceptor stimulations (99 +/- 17%, not significant) but did not modify the lusitropic responses to isoproterenol. Protamine abolis hed the inotropic responses to forskolin (89 +/- 6 vs. 154 +/- 20%, P < 0.0 5) and markedly decreased that of dibutyryl 3',5'-cAMP (132 +/- 31 vs. 167 +/- 30%, P < 0.05) but did not modify their lusitropic responses. Conclusions: Protamine abolished the inotropic responses to alpha- and beta -adrenoceptor stimulations but preserved the lusitropic responses to beta -adrenoceptor stimulation. Although protamine may act at several sites on t he adrenoceptor stimulation cascade, one of its main sites of action is sit uated downstream from cAMP-mediated phosphorylation.