Identification of alpha1-adrenoceptor subtypes in the human prostatic urethra

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