IDENTIFICATION, LOCALIZATION AND FUNCTIONAL-ANALYSIS OF IMIDAZOLINE AND ALPHA-ADRENERGIC RECEPTORS IN CANINE PROSTATE

In nonsurgical management of benign prostatic hyperplasia, drugs which interfere with prostate contraction mediated through the alpha-1 adre nergic receptor are used. Clonidine acts at alpha adrenergic and I-1-i midazoline receptors. In the present study, we found the K-d for [H-3] clonidine binding to I-1 sites in canine prostate to be 4 +/- 1 nM; th e B-max was 18 +/- 2 fmol/mg of protein. Inhibition of binding by imid azolines and by brain extracts containing putative endogenous ligand c onfirmed the identity of these sites as I-1-imidazoline. Autoradiograp hic studies showed localization of both I-1 and alpha-2 sites to the g landular epithelium. We sought to determine whether in vivo activation of the I-1-imidazoline sites by clonidine mediates its contractile ac tion in canine prostate. Dose-response curves were generated for para- aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 an tagonist), idazoxan (alpha2/l(1)/l(2) antagonist) and prazosin (alpha- 1 antagonist). Prazosin was the most effective antagonist. Yohimbine w as less effective and did not effectively discriminate between para-am inoclonidine and phenylephrine, an alpha-1-selective agonist. Idazoxan antagonized para-aminoclonidine, but by not more than 50% at any dose . These results suggest that clonidine is active primarily at alpha-1 receptors on prostate smooth muscle in vivo. Thus the function of the I-1 and alpha-2 receptors in the prostate remains to be determined; ho wever, they may be involved in epithelial cell function.