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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 norepinephrine (NE) caused concentration-dependent contractions that were partially and noncompetitively inhibited by 10 to 100 microM. of chloroethylclonidine (CEC), an alkylating agent that specifically and irreversibly inactivates alpha 1B-AR and alpha 1C-AR subtypes. Norepinephrine-induced contractions were competitively and effectively inhibited with WB 4101, a competitive, high-affinity antagonist for alpha 1A-AR and alpha 1C-AR subtypes. The CEC-insensitive receptor subtypes bound WB 4101 with high affinity, suggesting the presence of alpha 1A-AR in HCC. Binding of 3Hprazosin and 2-beta-(4-hydroxy-3-[125Iiodophenyl)-ethylaminomethyl]-tetralone (125IHEAT) to membranes of HCC treated with or without CEC demonstrated the presence of two subpopulations: a CEC-sensitive receptor population (40 to 50%), which may represent inactivation of the alpha 1B-AR and alpha 1C-AR subtypes, and a CEC-resistant receptor subpopulation, which is probably the alpha 1A-AR subtype. The physiological and biochemical properties of alpha 1-AR in HCC clearly suggest that the NE-induced contraction of HCC smooth muscle is mediated by more than one alpha 1-AR subtype. It is likely that two or possibly three receptor subtypes are involved in mediating the contraction. Further, it is possible that NE-mediated contraction of trabecular smooth muscle requires synergistic receptor-receptor receptor interactions at the second messenger or at the receptor protein level.
Traish et al. (Sun,) studied this question.