6-nitrodopamine (6-ND) is released from human umbilical cord vessels and modulates vascular reactivity by acting as a dopamine antagonist. Here we investigate whether 6-ND is released by the rat isolated vas deferens and its effect on this tissue. Dopamine, noradrenaline, adrenaline and 6-ND levels were quantified in rat isolated vas deferens by LC-MS-MS. Electric-field stimulation (EFS) and concentration-response curves to 6-ND, noradrenaline, dopamine and adrenaline were performed in the absence and in the presence (30 min) of L-NAME, SCH-23390, haloperidol, PG-01037, sonepiprazole, desipramine, clomipramine, amitriptyline, cyclobenzaprine, carbamazepine, maprotiline, paroxetine, oxcarbazepine and ketanserin in the rat isolated epididymal vas deferens (RIEVD). Basal releases of 6-ND and noradrenaline were detected from the rat isolated vas deferens. 6-ND release was reduced by tissue incubation with L-NAME and from the vas deferens obtained from L-NAME-treated rats. SCH-23390 caused leftward shifts on concentration-response curves to 6-ND without affecting dopamine- or EFS-induced RIEVD contractions. Haloperidol, PG-01037 and sonepiprazole caused significant rightward shifts on concentration-response curves to dopamine but had no effect on either the 6-ND or EFS-induced RIEVD contractions. The tricyclic compounds desipramine, clomipramine, amitriptyline, cyclobenzaprine and carbamazepine induced rightward shifts on 6-ND concentration-response curve but did not reduce the noradrenaline, dopamine and adrenaline contractile responses. They also reduced the EFS-induced RIEVD contractions in control but not in tissues obtained from L-NAME-treated animals. Maprotiline, oxcarbazepine, paroxetine and ketanserin had no effect in either 6-ND or EFS-induced RIEVD contractions. Thus, 6-ND modulates RIEVD contractility, and desipramine, clomipramine, amitriptyline, cyclobenzaprine and carbamazepine act as selective 6-ND receptor antagonists.
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