FUNCTIONAL IDENTIFICATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN HUMAN PROSTATE - COMPARISON WITH THOSE IN RAT VAS-DEFERENS AND SPLEEN

The effects of some alpha(1)-adrenoceptor antagonists (prazosin, nonselective for the alpha(1A)- and alpha(1B)-adrenoceptor subtypes; 5-methyl-urapidil, selective for the alpha(1A)-adrenoceptor subtype; chloroethylclonidine, selective for the alpha(1B)-adrenoceptor subtype) and nifedipine were compared on contractile responses to noradrenaline or phenylephrine in human prostatic tissues, rat vas deferens and spleen. In rat vas deferens, nifedipine (1 mu M), but not chloroethylclonidine (100 mu M), almost completely abolished noradrenaline-induced contraction, the pA(2) values for prazosin and 5-methyl-urapidil against noradrenaline being 9.29 and 8.55, respectively. In rat spleen, chloroethylclonidine reduced (by 57%) the maximum contraction induced by phenylephrine; nifedipine was ineffective. The log concentration-response curve was shifted significantly to the right; the pA(2) values of prazosin and 5-methyl-urapidil against phenylephrine were 9.45 and 7.21, respectively. In human prostatic tissues, both nifedipine and chloroethylclonidine produced significant inhibition of noradrenaline-induced contractions. Chloroethylclonidine produced a 44% reduction of the maximum contraction to noradrenaline and shifted the log concentration-response curve to the right. In contrast, nifedipine, while reducing the maximum response to a similar extent, produced a small rightward shift in the log concentration-response curve. The pA(2) values for prazosin and 5-methyl-urapidil against noradrenaline were 9.21 and 7.74, respectively. The pA(2) values for prazosin in these three tissues did not vary significantly, whereas that for 5-methyl-urapidil in human prostatic tissue was intermediate between that in rat vas deferens and that in rat spleen: these tissues contain primarily alpha(1A)- and alpha(1B)-adrenoceptor subtypes, respectively. These results indicate that noradrenaline-induced contractions in human prostatic tissue are mediated by both alpha(1A)- and alpha(1B)-adrenoceptor subtypes.