Objective: To characterize the alpha 1-adrenoceptor subtypes of the human benignly enlarged prostate using functional and binding studies.
Materials and methods: Strips of prostatic tissue taken from nine patients with benign prostatic hypertrophy who were undergoing open prostatectomy were used in the study.
Results: The strips isolated from five prostates produced a large contraction in response to noradrenaline and phenylephrine but not to clonidine. The contractile response induced by noradrenaline was competitively antagonized by representative alpha 1-adrenoceptor antagonists (prazosin, WB4101, 5-methylurapidil and HV723), the dissociation constants (pKB) being < 8.5. Pre-treatment with chloroethylclonidine was without effect on the contractile response to noradrenaline. In saturation experiments with five prostates, [3H]-prazosin bound to the prostate membranes with two distinct affinities (pKD = 9.95 +/- 0.07 and 8.71 +/- 0.04, Bmax = 151 +/- 8 and 138 +/- 3 fmol/mg protein, respectively). Unlabelled prazosin and WB4101 biphasically displaced the binding of 200 pM [3H]-prazosin; the resulting high and low pKI values for each of the antagonists were consistent with the two pKD values obtained for [3H]-prazosin in the saturation experiments. 5-Methylurapidil and HV723 displaced the [3H]-prazosin binding monophasically with an affinity (pKI) close to 8.5.
Conclusions: These results suggest the presence of at least two distinct alpha 1-adrenoceptor subtypes (presumably an alpha 1C subtype with a high affinity for prazosin and WB4101, and a putative alpha 1L subtype with a low affinity for the antagonists) in the human prostate, in which the latter subtype may be predominantly involved in the contractile response to noradrenaline.