A HETEROGENEOUS POPULATION OF ALPHA(1) ADRENERGIC-RECEPTORS MEDIATES CONTRACTION OF HUMAN CORPUS CAVERNOSUM SMOOTH-MUSCLE TO NOREPINEPHRINE

In this study we investigated the physiological properties and binding characteristics of alpha-1 adrenergic receptor (alpha(1)-AR) in human corpus cavernosum (HCC) in order to identify alpha(1)-AR subtypes at the functional protein level. Exposure of tissue strips to norepinephr ine (NE) caused concentration-dependent contractions that were partial ly and noncompetitively inhibited by 10 to 100 mu M. of chloroethylclo nidine (CEC), an alkylating agent that specifically and irreversibly i nactivates alpha(1B)-AR and alpha(1C)-AR subtypes. Norepinephrine-indu ced contractions were competitively and effectively inhibited with WB 4101, a competitive, high-affinity antagonist for alpha(1A)-AR and alp ha(1C)-AR subtypes. The CEC-insensitive receptor subtypes bound WB 410 1 with high affinity, suggesting the presence of alpha(1A)-AR in HCC. Binding of [H-3]prazosin and y-3-[I-125]iodophenyl)-ethylaminomethyl}- tetralone ([I-125]HEAT) to membranes of HCC treated with or without CE C demonstrated the presence of two subpopulations: a CEC-sensitive rec eptor population (40 to 50%), which may represent inactivation of the alpha(1B)-AR and alpha(1C)-AR subtypes, and a CEC-resistant receptor s ubpopulation, which is probably the alpha(1A)-AR subtype. The physiolo gical and biochemical properties of alpha(1)-AR in HCC clearly suggest that the NE-induced contraction of HCC smooth muscle is mediated by m ore than one alpha(1)-AR subtype. It is likely that two or possibly th ree receptor subtypes are involved in mediating the contraction. Furth er, it is possible that NE-mediated contraction of trabecular smooth m uscle requires synergistic receptor-receptor interactions at the secon d messenger or at the receptor protein level.