Identification of alpha1-adrenoceptor subtypes in the human prostatic urethra

To identify the α₁-adrenoceptor subtypes in the human prostatic urethra, we compared the potencies of various α₁-adrenoceptor agonists and antagonists in inhibiting [³H]tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the binding of (+)-β-([¹²⁵I]iodo-4-hydroxyphenyl)ethylaminomethyl-tetralone ([¹²⁵I]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 α₁-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 α₁-adrenoceptors. Prazosin showed lower affinity for α₁-adrenoceptors in the human prostatic urethra than for any of the three cloned α₁-adrenoceptors. Comparison of the affinities of α₁-adrenoceptor agonists and antagonists for human prostatic urethral α₁-adrenoceptors to their affinities for the three cloned α₁ subtypes indicated a close correlation between the affinities for human urethral α₁ and the cloned α_1a-adrenoceptors. However, prazosin did not conform to this pattern. These findings suggest that the predominant α₁-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. Received: 2 August 1996 / Accepted: 17 October 1996