Interaction of protamine with alpha- and beta-adrenoceptor stimulations in rat 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 (relaxation) response to beta-adrenoceptor stimulation remain unknown.


METHODS
The effects of protamine (10 or 100 microg/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 microm) 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 alpha- (102 +/- 23%, not significant) and beta-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 alpha- and beta-adrenoceptor stimulations but preserved the lusitropic responses to beta-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.
David
J S
JS
Department of Anesthesiology, Centre Hospitalier Univeristaire Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, France.
Vivien
B
B
Lecarpentier
Y
Y
Coriat
P
P
Riou
B
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D009126:Muscle Relaxation / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011479:Protamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta