The β-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue

Abstract

The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of β-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (K(D) about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similary to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.