Abstract

Catecholamines regulate lipolysis in rat fat cells via beta-adrenergic receptors. Recently, it has been proposed that beta-adrenergic receptors of rat fat cells are neither beta 1 nor beta 2 in character but rather an 'isoreceptor,' 'hybrid,' or 'beta 3' [Br. J. Pharmacol. 84:131-137 (1985)]. This putative receptor subtype has been envisioned as possessing an alkanolamine side-chain interaction site of beta 1 nature and an aromatic moiety interaction site of beta 2 nature. These proposals were evaluated in the present work through a reexamination of the nature of the fat cell beta-adrenergic receptor using four radioligands that differ chemically in one or both of these regions of the molecule as well as in their hydrophobicity. Equilibrium binding of agonist and of beta 1- and beta 2-subtype-selective high affinity antagonist ligands to fat cell membranes was detailed. The binding sites labeled by these ligands had the characteristics of beta 1-adrenergic receptors. The rank order of subtype-selective antagonists in competing for radioligand binding to fat cell membranes was the same as that for inhibition of agonist-stimulated cyclic AMP accumulation by these ligands. At equimolar concentrations, the beta 1-selective antagonist CGP-20712A provided a greater degree of inhibition of catecholamine-stimulated lipolysis than the beta 2-selective antagonist ICI-118,551. These results document the character of the rat fat cell beta-adrenergic receptor as solely beta 1.