PHARMACOLOGICAL EVIDENCE OF DISTINCT ALPHA(1)-ADRENOCEPTOR SUBTYPES MEDIATING THE CONTRACTION OF HUMAN PROSTATIC URETHRA AND PERIPHERAL ARTERY

1 The alpha(1)-adrenoceptor subtypes mediating contractions of the smooth muscle in human prostatic urethra and branches of internal iliac artery were characterized in isometric contraction experiments. 2 Phenylephrine produced concentration-dependent contractions in both the urethra and artery. These responses were competitively inhibited by prazosin, WB4101 and 5-methyl-urapidil, and the slopes of Schild plots for all these antagonists were close to unity. 3 The pA(2) values for prazosin were not significantly different between the urethra (9.42 +/- 0.11; mean +/- s.d.) and artery (9.50 +/- 0.27), while the pA(2) values for WB4101 and 5-methyl-urapidil in the human prostatic urethra (8.94 +/- 0.19 and 8.42 +/- 0.14, respectively) were significantly greater than in the branches of human internal iliac artery (7.94 +/- 0.21 and 7.43 +/- 0.22, respectively; P < 0.01). 4 Pretreatment with chlorethylclonidine (CEC) at concentrations ranging from 0.1 mu M to 100 mu M attenuated the maximum contraction to phenylephrine in a concentration-dependent manner in both the urethra and artery. However, the urethra was significantly less affected by CEC than the artery. The pD'(2) values (negative logarithm of the molar concentration of antagonist which reduced the maximum contraction to one half) in the urethra and artery were 4.35 +/- 0.27 and 5.20 +/- 0.37, respectively (P < 0.01). 5 The present results indicate that there are distinct populations of alpha(1)-adrenoceptor subtypes in the human prostatic urethra and branches of the internal iliac artery. The alpha(1)-adrenoceptors responsible for the contraction of the human internal iliac artery branches are predominantly alpha(1B)-subtype, whereas thosein the human prostatic urethra are considered to be not alpha(1B), but alpha(1C) or possibly alpha(1A) or alpha(1A)/(D)-subtype.