DISCRIMINATION BETWEEN ALPHA-2-ADRENOCEPTORS AND [H-3] IDAZOXAN-LABELED NONADRENERGIC SITES IN RABBIT WHITE FAT-CELLS

Previous results indicated that the rabbit could represent a suitable model for investigations on the functional role of alpha-2-adrenoceptors in fat cells, but the characterization of these receptors was not resolved yet. In the present report, imidazoline compounds were used to attempt a better definition of rabbit adipocyte alpha-2-receptivity by means of lipolysis and binding studies. Lipolysis data showed that UK14304 is a full alpha-2-adrenoceptor agonist promoting a strong antilipolysis in rabbit fat cells. Moreover, the methoxy derivative of idazoxan, RX821002, is a more potent antagonist of UK14304-induced antilipolysis than idazoxan or yohimbine. Whereas [H-3]yohimbine failed to bind at rabbit adipocyte alpha-2-adrenoceptors, [H-3]UK14304 and [H-3]RX821002 are valuable tools to study this receptor. Analysis of binding data demonstrated that [H-3]UK14304 labels the high-affinity-state receptor while [H-3]RX821002 binds to the whole alpha-2-adrenergic population. Inhibition studies of [H-3]RX821002 and [H-3]UK14304 binding by various compounds confirmed the alpha-2-adrenergic nature of the sites labelled by both radioligands. The other alpha-2-adrenoceptor radioligand, [H-3]idazoxan, labelled binding sites which are insensitive to catecholamines. Competition studies of [H-3]idazoxan binding with imidazoline derivatives revealed structure-activity relationships different from those of alpha-2-adrenoceptors. The most striking observation is that substitutions in the 2-position of idazoxan markedly reduce the affinity for the non-adrenergic sites, whereas the alpha-2-potency is increased or unchanged.