Alpha1-adrenergic antagonists block 6-nitrodopamine contractions on the rat isolated epididymal vas deferens

Abstract

6-nitrodopamine (6-ND) is released from rat isolated vas deferens and modulates electrical-field stimulation (EFS) contractions of the rat isolated epididymal vas deferens (RIEVD) via a specific receptor which is blocked by tricyclic antidepressants. Here, the effects of selective α1-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline and EFS were investigated. Doxazosin and tamsulosin (3–10 nM) caused significant rightward shifts of the concentration-response curve to 6-ND, but had no effect on dopamine-, noradrenaline- and adrenaline-induced contractions. Alfuzosin (10 nM) produced rightward shifts on concentration-response curves to all catecholamines. Silodosin (10 nM) and terazosin (100 nM) displaced to the right the noradrenaline, dopamine and adrenaline curves, but higher concentrations of both antagonists (100 and 300 nM, respectively) were required to displace the 6-ND curves. The EFS-induced contractions were significantly inhibited only at the concentrations that the α1-adrenergic receptor antagonists caused rightward shifts on the 6-ND concentration-response curves. The inhibition of EFS-induced contractions by doxazosin (10 nM), tamsulosin (10 nM), alfuzosin (10 nM), silodosin (100 nM) and terazosin (300 nM), were not observed in RIEVD obtained from animals chronically treated with L-NAME. This work demonstrates that α1-adrenoceptor antagonists act as 6-ND receptor antagonists in RIEVD, opening the possibility that many actions previously attributed to noradrenaline could be due to 6-ND antagonism. In addition, blockade of the 6-ND receptors by both tricyclic antidepressants and α1-adrenergic receptor antagonists may represent the common mechanism of action responsible for their therapeutic use in the treatment of premature ejaculation.