I. Muramatsu et al., PHARMACOLOGICAL CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES INTHE HUMAN PROSTATE - FUNCTIONAL AND BINDING-STUDIES, British Journal of Urology, 74(5), 1994, pp. 572-578
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.