Identification of alpha 1-adrenoceptor subtypes in the human prostatic urethra.

To identify the alpha 1-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various alpha 1-adrenoceptor agonists and antagonists in inhibiting [3H]tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of (+)-beta-([125I]iodo-4-hydroxyphenyl)ethylaminomethyl-tetralone ([125I]HEAT) to cloned human alpha 1a, alpha 1b and alpha 1d subtypes. The alpha 1A-selective antagonists 5-methylurapidil and (+)niguldipine showed higher affinities for both cloned alpha 1a and urethral alpha 1-adrenoceptors than for cloned alpha 1b- and alpha 1d-adrenoceptors. NS-49, (R)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, recently characterized as an alpha 1A-selective agonist, also showed high affinity for the cloned alpha 1a subtype and urethral alpha 1-adrenoceptors. Prazosin showed lower affinity for alpha 1-adrenoceptors in the human prostatic urethra than for any of the three cloned alpha 1-adrenoceptors. Comparison of the affinities of alpha 1-adrenoceptor agonists and antagonists for human prostatic urethral alpha 1-adrenoceptors to their affinities for the three cloned alpha 1 subtypes indicated a close correlation between the affinities for human urethral alpha 1 and the cloned alpha 1a-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant alpha 1-adrenoceptor in the human urethra is the alpha 1A subtype, and that an alpha 1L subtype which has been characterised by its low affinity for prazosin, may also be present.