title: Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate.
abstract: In nonsurgical management of benign prostatic hyperplasia, drugs which interfere with prostate contraction mediated through the alpha-1 adrenergic receptor are used. Clonidine acts at alpha adrenergic and I1-imidazoline receptors. In the present study, we found the Kd for [3H]clonidine binding to I1 sites in canine prostate to be 4 +/- 1 nM; the Bmax was 18 +/- 2 fmol/mg of protein. Inhibition of binding by imidazolines and by brain extracts containing putative endogenous ligand confirmed the identity of these sites as I1-imidazoline. Autoradiographic studies showed localization of both I1 and alpha-2 sites to the glandular epithelium. We sought to determine whether in vivo activation of the I1-imidazoline sites by clonidine mediates its contractile action in canine prostate. Dose-response curves were generated for para-aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha-2/I1/I2 antagonist) and prazosin (alpha-1 antagonist). Prazosin was the most effective antagonist. Yohimbine was less effective and did not effectively discriminate between para-aminoclonidine 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 I1 and alpha-2 receptors in the prostate remains to be determined; however, they may be involved in epithelial cell function.
authors.affiliation: James Buchanan Brady Foundation, Department of Urology, New York Hospital-Cornell University Medical College, New York.
authors.forename: D
authors.initials: D
authors.lastname: Felsen
authors.forename: P
authors.initials: P
authors.lastname: Ernsberger
authors.forename: P M
authors.initials: PM
authors.lastname: Sutaria
authors.forename: R J
authors.initials: RJ
authors.lastname: Nejat
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: May
authors.forename: D S
authors.initials: DS
authors.lastname: Breslin
authors.forename: D N
authors.initials: DN
authors.lastname: Marion
authors.forename: E D
authors.initials: ED
authors.lastname: Vaughan
mesh_terms: D000818:Animals; D001345:Autoradiography; D001381:Azepines / Q000494:pharmacology; D001665:Binding Sites; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D008297:Male; D011467:Prostate / Q000737:chemistry*; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D011955:Receptors, Drug / Q000032:analysis*
chemical_list: D001381:Azepines; D007093:Imidazoles; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D006165:Guanylyl Imidodiphosphate; C024763:talipexole; C016986:apraclonidine; C043482:moxonidine; D003000:Clonidine