PHARMACOLOGICAL CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES INTHE HUMAN PROSTATE - FUNCTIONAL AND BINDING-STUDIES

Objective To characterize the alpha(1)-adrenoceptor subtypes of the hu man benignly enlarged prostate using functional and binding studies. M aterials and methods Strips of prostatic tissue taken from nine patien ts with benign prostatic hypertrophy who were undergoing open prostate ctomy were used in the study. Results The strips isolated from five pr ostates produced a large contraction in response to noradrenaline and phenylephrine but not to clonidine. The contractile response induced b y noradrenaline was competitively antagonized by representative alpha( 1)-adrenoceptor antagonists (prazosin, WB4101, 5-methylurapidil and HV 723), the dissociation constants (pK(B)) being <8.5. Pre-treatment wit h chloroethylclonidine was without effect on the contractile response to noradrenaline. In saturation experiments with five prostates, [H-3] -prazosin bound to the prostate membranes with two distinct affinities (pK(D) = 9.95+/-0.07 and 8.71+/-0.04, Bmax = 151+/-8 and 138+/-3 fmol /mg protein, respectively). Unlabelled prazosin and WB4101 biphasicall y displaced the binding of 200 pM [H-3]-prazosin; the resulting high a nd low pK(I) values for each of the antagonists were consistent with t he two pK(D) values obtained for [H-3]-prazosin in the saturation expe riments. 5-Methylurapidil and HV723 displaced the [H-3]-prazosin bindi ng monophasically with an affinity (pK(I)) close to 8.5. Conclusions T hese results suggest the presence of at least two distinct alpha(1)-ad renoceptor subtypes (presumably an alpha(1C) subtype with a high affin ity for prazosin and WB4101, and a putative alpha(IL) subtype with a l ow affinity for the antagonists) in the human prostate, in which the l atter subtype may be predominantly involved in the contractile respons e to noradrenaline.