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 ag onists and antagonists in inhibiting [H-3]tamsulosin binding to human prostatic urethral membranes with their potencies in inhibiting the bi nding of eta-([I-125]iodo-4-hydroxyphenyl)ethylaminomethyl- tetralone ([I-125]HEAT) to cloned human alpha(1a), alpha(1b) and alpha(1d) subty pes. The alpha(1A)-selective antagonists 5-methylurapidil and (+)nigul dipine showed higher affinities for both cloned alpha(1a) and urethral alpha(1)-adrenoceptors than for cloned alpha(1b)- and alpha(1d)-adren oceptors. NS-49, mino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hy drochloride, recently characterized as an alpha(1A)-selective agonist, also showed high affinity for the cloned alpha(1a) subtype and urethr al alpha(1)-adrenoceptors. Prazosin showed lower affinity for alpha(1) -adrenoceptors in the human prostatic urethra than for any of the thre e 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. Howeve r, prazosin did not conform to this pattern. These findings suggest th at the predominant alpha(1)-adrenoceptor in the human urethra is the a lpha(1A) subtype, and that an alpha(1L) subtype which has been charact erised by its low affinity for prazosin, may also be present.