Differential coupling to positive inotropic responses of cyclic AMP produced by stimulation of beta 1- and beta 2-adrenergic receptors.

Abstract

In canine right ventricular muscle, isoproterenol, a nonselective beta-agonist, and T-1583, a selective beta 1-agonist, produced positive inotropic effects (PIE) as full agonists. Their PIEs were antagonized by atenolol, a selective beta 1-antagonist, (pA2 = 7.71 for isoproterenol and pA2 = 7.82 for T-1583). The PIE of T-1583 was also antagonized by practolol, a selective beta 1-antagonist (pA2 = 6.55). Procaterol known as a selective beta 2-agonist gave a biphasic concentration-response curve with a maximum that was approximately half those of isoproterenol and T-1583. The PIE of procaterol at low concentrations (pD2 = 7.93), which maximum was approximately 10% of the maximum of isoproterenol, was antagonized by ICI 118,551, a selective beta 2-antagonist (ICI; pA2 = 8.84) and that at high concentrations (pD2 = 5.12) by atenolol (pA2 = 7.56). Increases in cyclic AMP content produced by isoproterenol were reduced greatly by atenolol and slightly by ICI, whereas those produced by T-1583, which were smaller than those by isoproterenol, were abolished by atenolol but not changed by ICI. Procaterol (10(-7) M) produced an increase in cyclic AMP, which was abolished by ICI but not changed by atenolol, to almost the same extent as procaterol (10(-5) M) did, which was abolished by atenolol and slightly reduced by ICI. These results indicate that increased cyclic AMP through beta 1- but not beta 2-receptors couples well to PIE.