Differential coupling to positive inotropic responses of cyclic AMP produced by stimulation of β₁- and β₂-adrenergic receptors

In canine right ventricular muscle, isoproterenol, a nonselective β-agonist, and T-1583, a selective β₁-agonist, produced positive inotropic effects (PIE) as full agonists. Their PIEs were antagonized by atenolol, a selective β₁-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 β₁-antagonist (pA₂ = 6.55). Procaterol known as a selective β₂-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 ~10% of the maximum of isoproterenol, was antagonized by ICI 118,551, a selective β₂-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 β_1- but not β₂-receptors couples well to PIE.