CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN PROSTATE AND PROSTATIC URETHRA OF RAT, RABBIT, DOG AND MAN

The alpha(1)-adrenoceptor subtypes present in the smooth muscle of ure thra and prostate of different animal species, including man, were cha racterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [H-3]prazosin labelled a single population of alpha(1)-adrenoceptors (Hill coefficient not different from unity) wit h a high affinity in the range 0.21-0.51 nM. The number of specific [H -3]prazosin binding sites was partially affected by chloroethylclonidi ne only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes a s well as in the prostatic urethra membranes of air the animal species examined. These findings indicate that in prostatic and urethral memb ranes the alpha(1)-adrenoceptors mainly belong to the alpha(1A) subtyp e. The binding results were confirmed by in vitro functional studies o n noradrenaline-induced contractions of rabbit and dog urethral prepar ations. The agonist-induced contractions were practically unaffected b y preincubation of both tissues with chloroethylclonidine, but were se nsitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha(1)-adrenoce ptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contra ctions of rabbit urethra and their affinity for the alpha(1A)-adrenoce ptor subtype, no correlation with the affinity for the alpha(1)B subty pe, and a lower correlation with the affinity for the alpha(1C)-adreno ceptor subtype.