Alpha1-adrenergic antagonists act as 6-nitrodopamine receptor antagonists in the human vas deferens

Abstract

Abstract Background: 6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α1-adrenoceptor antagonists is associated with ejaculatory abnormalities. Objectives: To evaluate the effect of α1-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD). Methods: HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit’s solution. Cumulative concentration-response curves to catecholamines (10 nM-300 mM) were constructed in HEVD strips pre-incubated (30 min) with doxazosin (0.1-1nM), tamsulosin (1-10 nM), prazosin (10-100 nM) and/or silodosin (0.1-10 nM). The effects of these α1-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32 Hz)-induced contractions. Results: Doxazosin (0.1 nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1 nM) and prazosin (10 nM). At these concentrations, these α1-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1 nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1 nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1 nM, but not at 0.1 nM, caused significant reductions in the EFS-induced contractions. Discussion and conclusion: The results indicate that 6-ND plays a major role in the human vas deferens contractility and doxazosin, tamsulosin, prazosin and silodosin cause ejaculation disorders in man by blocking the 6-ND receptor rather than α1-adrenoceptors.