EXPRESSION OF I-2-IMIDAZOLINE SITES IN RAT PROSTATE - EFFECT OF CASTRATION AND AGING

Clonidine, idazoxan, and related imidazoline adrenergic drugs bind to non-adrenergic sites in brain and several peripheral tissues. These si tes, termed imidazoline receptors, appear to exist in two major subcla sses, I-1 sites labeled by clonidine and I-2 sites labeled by idazoxan . In this study, we investigated whether rat prostate expresses imidaz oline receptors and, if so, whether their expression can be regulated by circulating testosterone. Studies in rat ventral prostate membrane revealed that [H-3]idazoxan, but not [H-3]P-aminoclonidine, bound to n on-adrenergic sites. The binding of [H-3]idazoxan was saturable (B-max : 941 +/- 105 fmol/mg protein) and high affinity (K-D: 16.4 +/- 2.3 nM ). The rank order of the inhibition of binding by imidazoline ligands was cirazoline > clonidine > UK 14,304 > guanabenz, indicating an I-2 subclass of imidazoline receptors. Bilateral orchiectomy increased the number of binding sites (B-max) for [H-3]idazoxan without changing th e affinity (K-D). Testosterone replacement, while completely restoring the plasma testosterone levels, only partially B-max. In contrast, th e binding of [H-3]idazoxan to prostate membranes of rats in different reversed the increase in B age groups (4, 7, and 16 months) revealed a progressive decrease in the B-max without any change in K-D. We concl ude that the rat prostate expresses the I-2 subclass of imidazoline re ceptors and that the expression is regulated by circulating testostero ne.