CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN TENSION RESPONSE OF HUMAN PROSTATE TO ELECTRICAL-FIELD STIMULATION

1 The effects of various alpha(1)-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2 Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical held stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 mu M, blocked these effects by only 50%. 3 The contractile responses of rat vas deferens and spleen to exogenously-applied alpha(1)-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA(2) values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha(1A)-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha(1B)-adrenoceptors. 4 Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical held stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 mu M), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5 The involvement of prejunctional alpha(2)-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10(-9) to 3 x 10(-7) M) blocked concentration-dependently the contractile response to electrical held stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10(-7) M). Additionally, the inhibitory effect of CEC (3 x 10(-6) to 3 x 10(-4) M) to the nerve-mediated contraction was also partially reversed by yohimbine (10(-7) M). 6 It is suggested that the putative alpha(1)A-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha(1B) and/or alpha(1C)-adrenoceptors exist in this region.