ALPHA(1)-ADRENOCEPTOR SUBTYPE IN THE RAT PROSTATE IS PREFERENTIALLY THE ALPHA-1A TYPE

Alpha1-Adrenoceptors in the rat prostate were characterized by a binding assay using the newly synthesized radioligand [H-3]-YM617 (5-[2-[[2[ethoxyring(n)-H-3](o-ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide HCl) and an in vitro assay. Specific [H-3]-YM617 binding in the rat prostate was saturable and of high affinity (K(D) = 61.5 +/- 5.9 pM) with 23.2 +/- 6.9 fmol/mg of protein as the maximal number of binding sites (B(max)). Alpha-Adrenoceptor agonists and antagonists inhibited the binding of the radioligand with the following order of effectiveness: YM617 > prazosin = bunazosin > WB4101 > 5-methylurapidil = phenoxybenzamine > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine. Alpha1-Adrenoceptors in the rat prostate preferred the R(-)-isomer of YM617 to the S(+)-isomer. Preincubation with chlorethylclonidine (CEC; 10(-5) M, 10 min) just slightly changed the B(max) value for [H-3]-YM617 without changing the K(D) value in the prostate; however, CEC reduced the B(max) in the aorta. In the isolated tissue, pretreatment with CEC (10(-5) M, 10 and 30 min) time-dependently shifted to the right the dose-response curve for phenylephrine and decreased the maximal contraction of aortas induced by phenylephrine, but did not shift or decrease those of prostates. The present results indicate that the alpha1-adrenoceptors in the rat prostate are mainly CEC-insensitive (alpha1A), whereas those in the aorta are CEC-sensitive (alpha1B).