Mg2+ efflux from the isolated perfused rabbit heart is mediated by two states of the beta1-adrenergic receptor.

The non-selective beta-adrenergic receptor agonist isoproterenol stimulates Mg(2+) efflux from the perfused heart. The beta-adrenergic receptor subtype governing Mg(2+) efflux was determined in rabbit hearts perfused by the method of Langendorff with Mg(2+)-free Krebs Henseleit buffer. Magnesium efflux was examined during infusion of isoproterenol (a non-selective beta-adrenergic agonist), dobutamine (beta(1)-selective), salbutamol (beta(2)-selective), BRL37344 in the presence of 200 nM propranolol (beta(3)-selective conditions) or CGP12177 (beta(3)/low affinity state beta(1)-selective). Isoproterenol increased Mg(2+) efflux in a dose-dependent manner, and was the most potent and efficacious agent used. Dobutamine and CGP12177 each significantly increased Mg(2+) efflux, but with markedly different time characteristics. Dobutamine induced significantly less Mg(2+) release than isoproterenol. Although the maximal effect of CGP12177 on Mg(2+) release was 30% less than that of isoproterenol, the difference was not statistically significant. Neither salbutamol nor BRL37344 had any effect on Mg(2+) efflux. These results suggest that isoproterenol-induced Mg(2+) efflux is mediated by both the high and low affinity states of the beta(1)AR, with the low affinity state making the larger contribution.