Mg2+ efflux from the isolated perfused rabbit heart is mediated by two states of the ß1-adrenergic receptor

The non-selective ß-adrenergic receptor agonist isoproterenol stimulates Mg2+ efflux from the perfused heart. The ß-adrenergic receptor subtype governing Mg2+ efflux was determined in rabbit hearts perfused by the method of Langendorff with Mg2+-free Krebs Henseleit buffer. Magnesium efflux was examined during infusion of isoproterenol (a non-selective ß-adrenergic agonist), dobutamine (ß1-selective), salbutamol (ß2-selective), BRL37344 in the presence of 200 nM propranolol (ß3-selective conditions) or CGP12177 (ß3/low affinity state ß1-selective). Isoproterenol increased Mg2+ efflux in a dose-dependent manner, and was the most potent and efficacious agent used. Dobutamine and CGP12177 each significantly increased Mg2+ efflux, but with markedly different time characteristics. Dobutamine induced significantly less Mg2+ release than isoproterenol. Although the maximal effect of CGP12177 on Mg2+ release was 30% less than that of isoproterenol, the difference was not statistically significant. Neither salbutamol nor BRL37344 had any effect on Mg2+ efflux. These results suggest that isoproterenol-induced Mg2+ efflux is mediated by both the high and low affinity states of the ß1 AR, with the low affinity state making the larger contribution