Further characterization of the myocardial α-adrenoceptors mediating positive inotropic effects in the rabbit myocardium

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Abstract

[3H]Prazosin bound with high affinity to the membrane fraction derived from the rabbit ventricular myocardium. Oxymetazoline displaced [3H]prazosin from its binding site, did not elicit a positive inotropic effect but antagonized the positive inotropic effect of phenylephrine mediated by α-adrenoceptors in the presence of a β-antagonist. Naphazoline was more potent in displacing [3H]prazosin and behaved as a weak partial agonist. YM-12617 (5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]2-methoxybenzenesulfonamide HCl), a potent selective α1-antagonist, displaced [3H]prazosin and antagonized the α-mediated postive inotropic effect with equal potency. Thus, a good correlation was found between the potency of α-antagonists to displace [3H]prazosin and their ability to antagonize the α-mediated positive inotropic effect. On the other hand, there was no significant correlation between the Ki and the pD2 value of the α-agonists (norepinephrine, epinephrine, phenylephrine and naphazoline), indicating that there is a non-linear relationship between agonist binding to myocardial α1-adrenoceptors and subsequent functional changes. Myocardial α1-adrenoceptors showed some pharmacological characteristics which appear to be different from those in smooth muscle tissues.

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