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.
Young
Lindon
L
Division of Pharmacology, Philadelphia College of Pharmacy at the University of the Sciences in Philadelphia, PA, USA.
Bercute-Dammann
Andrea
A
Weis
Margaret T
MT
D058665:Adrenergic beta-1 Receptor Agonists; D000818:Animals; D006321:Heart / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D010477:Perfusion / Q000379:methods*; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
D058665:Adrenergic beta-1 Receptor Agonists; D018342:Receptors, Adrenergic, beta-1; D008274:Magnesium; D007545:Isoproterenol