DIFFERENCES IN THE REGULATION OF [H-3] IDAZOXAN AND [H-3] YOHIMBINE BINDING-SITES IN THE RABBIT

In vitro studies suggest that [3H]yohimbine binds to α2-adrenoceptors while [3H]idazoxan binds preferentially at a non-adrenergic site. In order to compare in vitro with in vivo effects male New Zealand White rabbits received the following treatments: 5 days idazoxan 1.1 mg/kg per h, 10 days noradrenaline 46 μg/kg per h (intravenous infusion), 21 days amitriptyline 30 mg/kg per day (intraperitoneally) or vehicle. The effect of these treatments on the number of [3H]yohimbine and [3H]idazoxan binding sites was examined. Ten days noradrenaline infusion and 21 days amitripytyline treatment significantly reduced [3H]yohimbine binding in kidney and hindbrain membranes respectively, but had no significant effect on [3H]idazoxan binding. Five days idazoxan infusion significantly increased [3H]yohimbine binding in the forebrain, while a significant reduction in [3H]idazoxan binding sites in the kidney was observed. Thus differential regulation of the two binding sites was observed in vivo. These alterations in binding site number are consistent with the differing affinities of noradrenaline and idazoxan for the [3H]yohimbine and [3H]idazoxan binding sites previously observed in vitro and support the hypothesis that in the rabbit idazoxan binds preferentially at non-adrenergic sites while yohimbine binds to an α2-adrenergic site. The idazoxan site may be an imidazoline type of receptor but further work, including functional studies, is required to substantiate this. © 1990.