Expression of I2-imidazoline sites in rat prostate

Clonidine, idazoxan, and related imidazoline adrenergic drugs bind to non-adrenergic sites in brain and several peripheral tissues. These sites, termed imidazoline receptors, appear to exist in two major subclasses, I1 sites labeled by clonidine and I2 sites labeled by idazoxan. In this study, we investigated whether rat prostate expresses imidazoline receptors and, if so, whether their expression can be regulated by circulating testosterone. Studies in rat ventral prostate membrane revealed that [3H]idazoxan, but not [3H]p-aminoclonidine, bound to non-adrenergic sites. The binding of [3H]idazoxan was saturable (Bmax: 941 +/- 105 fmol/mg protein) and high affinity (KD: 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 I2 subclass of imidazoline receptors. Bilateral orchiectomy increased the number of binding sites (Bmax) for [3H]idazoxan without changing the affinity (KD). Testosterone replacement, while completely restoring the plasma testosterone levels, only partially reversed the increase in Bmax. In contrast, the binding of [3H]idazoxan to prostate membranes of rats in different age groups (4, 7, and 16 months) revealed a progressive decrease in the Bmax without any change in KD. We conclude that the rat prostate expresses the I2 subclass of imidazoline receptors and that the expression is regulated by circulating testosterone.