SUMMARY

selectivity of alpha-adrenergic antagonists: comparison of selective and nonselective radioligands. Mol. Pharmacol. 20:28-34 (1981). The alphai/alpha2-adrenergic receptor subtype selectivity of twelve adrenergic antago-mists was assessed by two different radioligand binding approaches in rabbit uterine membranes which contain both receptor subtypes. In the first approach, a nonsubtype selective antagonist radioligand, [3Hjdihydroergocryptine ([3H]DHE), was used to label all of the alpha-receptors. Selective competing ligands produced complex competition curves which could be analyzed by nonlinear least-squares curve-fitting methods to yield the Kd values of the competitor for the alphai- and alpha2-receptors, respectively. The second approach utilized the raclioligand antagonists [3Hlprazosin and [H]yohimbine. [3H]Prazosin was found to label alpha1-receptors, whereas [ H]yohimbine labeled alpha2-receptors. Competition experiments performed with subtype selective antagonists with these radioligands produced steep umphasic competition curves in all cases. Dissociation constants of drugs for the [3Hjprazosin and [3Hjyohimbine sites correlated highly with the alpha1 and alpha2 components of the complex [3H]DHE competition curves, respec-tively. Good quantitative agreement between the two sets of data was obtained, indicating the validity of both approaches for the determination of receptor subtype affinities. Nonetheless, use of subtype selective radioligands offered several advantages. When the nonsubtype selective radioligand [3H]DHE was used in this system, 100-fold selectivity of a competitor was required in order to determine reliably alphai and alpha2 affinities. In contrast, use of the selective radioligands discriminated much smaller degrees of selectivity without the necessity for sophisticated computer analysis of the data