FUNCTIONAL-CHARACTERIZATION OF ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE PROSTATIC URETHRA AND TRIGONE OF MALE RABBIT

The effects of alpha-1-adrenoceptor antagonists on the concentration-r esponse curves (CRC) to phenylephrine and oxymetazoline have been stud ied in prostatic urethra and trigone of male adult rabbits (28 wk old) . WB4101 and phentolamine, at low concentrations which should preferen tially antagonize the alpha-1A-adrenoceptor subtype, did not modify th e oxymetazoline-induced contraction of both prostatic urethra and trig one, suggesting that alpha-1A-adrenoceptors are not activated under th ese conditions. In urethra, pretreatment with 50 mu M chloroethylcloni dine (CEC), significantly reduced the maximal contraction to both agon ists to 60 and 70% of control, respectively. In trigone, CEC decreased the maximum contraction to phenylephrine, but not to oxymetazoline, b y 50%. In addition, CEC shifted to the right the CRC to both agonists. These results suggest the presence of an alpha-1B-adrenoceptor in bot h rabbit urethra and trigone. Exposure to prazosin (0.01-1 mu M) signi ficantly shifted to the right the CRC to phenylephrine (pA(2) or affin ity values without CEC treatment: 7.77 and 7.96 in urethra and trigone respectively; with CEC pretreatment: 7.49 and 7.42, respectively). Wh en oxymetazoline was used as an agonist and in the presence of CEC, pr azosin was unexpectedly weak in urethra with an affinity value of 6.70 , although the antagonist potency was not modified in trigone (affinit y 7.38). These values suggest that alpha-1-adrenoceptor agonists contr act rabbit urethra and trigone through activation of alpha-1-adrenocep tors displaying low affinity for prazosin. Whether this receptor coinc ides with the alpha-1L- or alpha-1N-subtype remains to be clarified.