6-Nitrodopamine is an endogenous mediator of rat isolated epididymal vas deferens contractions induced by electric-field stimulation

José Britto-Júnior; Luiz Ximenes; André Ribeiro; Adriano Fregonesi; Rafael Campos; Luiz Ricardo de Almeida Kiguti; Fabíola Z Mónica; Edson Antunes; Gilberto De Nucci

doi:10.1016/j.ejphar.2021.174544

6-Nitrodopamine is an endogenous mediator of rat isolated epididymal vas deferens contractions induced by electric-field stimulation

Eur J Pharmacol. 2021 Nov 15:911:174544. doi: 10.1016/j.ejphar.2021.174544. Epub 2021 Oct 1.

Authors

José Britto-Júnior¹, Luiz Ximenes², André Ribeiro², Adriano Fregonesi², Rafael Campos³, Luiz Ricardo de Almeida Kiguti⁴, Fabíola Z Mónica², Edson Antunes², Gilberto De Nucci⁵

Affiliations

¹ Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), São Paulo, Campinas, Brazil. Electronic address: josebrittojr@gmail.com.
² Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), São Paulo, Campinas, Brazil.
³ Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Superior Institute of Biomedical Sciences, Ceará State University (UECE), Fortaleza, Brazil.
⁴ Metropolitan University of Santos (UNIMES), Santos, Brazil.
⁵ Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), São Paulo, Campinas, Brazil; Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Metropolitan University of Santos (UNIMES), Santos, Brazil; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.

PMID: 34606837
DOI: 10.1016/j.ejphar.2021.174544

Abstract

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.

Keywords: Carbamazepine; Cyclobenzaprine; Dopamine; Ejaculation; Nitric oxide; Tricyclic antidepressants.

MeSH terms

Animals
Male
Rats
Vas Deferens*