Subclassification of β-adrenergic receptors of rat fat cells: A re-evaluation

Catecholamines regulate lipolysis in rat fat cells via β-adrenergic receptors. Recently, it has been proposed that β-adrenergic receptors of rat fat cells are neither β₁ nor β₂ in character but rather than an 'isoreceptor', 'hybrid', or 'β₃' [Br. J. Pharmacol. 84:131-137 (1985)]. This putative receptor subtype has been envisioned as possessing an alkanolamine side-chain interaction site of β₁ nature and an aromatic moiety interaction site of β₂ nature. These proposals were evaluated in the present work through a reexamination of the nature of the fat cell β-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 β₁- and β₂ subtype-selective high affinity antagonist ligands to fat cell membranes was detailed. The binding sites labeled by these ligands had the characteristics of β₁-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 β₁-selective antagonist CGP-20712A provided a greater degree of inhibition of catecholamine-stimulated lipolysis than the β₂-selective antagonist ICI-118,551. These results document the character of the rat fat cell β-adrenergic receptor as solely β₁.