Interaction of protamine with α and β-adrenoceptor stimulations in rat myocardium

Abstract

Background: Protamine alters the inotropic responses to β-adrenoceptor stimulation, but its mechanism of action is not well-understood. Moreover, its interaction with α-adrenoceptor stimulation and the lusitropic (relaxation) response to β-adrenoceptor stimulation remain unknown. Methods: The effects of protamine (10 or 100 μg/ml) on the responses induced 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 μM) and dibutyryl 3′,5′-cAMP (0.5 mM). Data are mean percentage of baseline active force ± SD. Results: In control groups, phenylephrine (135 ± 17%, P < 0.05) and isoproterenol (185 ± 44%, P < 0.05) induced a positive inotropic effect. Isoproterenol induced positive lusitropic effects under low and high loads. Protamine abolished the inotropic responses to α- (102 ± 23%, not significant) and β-adrenoceptor stimulations (99 ± 17%, not significant) but did not modify the lusitropic responses to isoproterenol. Protamine abolished the inotropic responses to forskolin (89 ± 6 vs. 154 ± 20%, P < 0.05) 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 α and β-adrenoceptor stimulations but preserved the lusitropic responses to β-adrenoceptor stimulation. Although protamine may act at several sites on the adrenoceptor stimulation cascade, one of its main sites of action is situated downstream from cAMP-mediated phosphorylation.