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

Autor(es)

Britto-Junior, Jose ^[1] ; Ximenes, Luiz ^[1] ; Ribeiro, Andre ^[1] ; Fregonesi, Adriano ^[1] ; Campos, Rafael ^{[2, 3]} ; Kiguti, Luiz Ricardo de Almeida ^[4] ; Monica, Fabiola Z. ^[1] ; Antunes, Edson ^[1] ; De Nucci, Gilberto ^{[5, 1, 2, 4]}

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil

^[2] Fed Univ Ceara UFC, Drug Res & Dev Ctr, Clin Pharmacol Unit, Fortaleza, CE - Brazil

^[3] Ceara State Univ UECE, Super Inst Biomed Sci, Fortaleza - Brazil

^[4] Metropolitan Univ Santos UNIMES, Santos - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 911, NOV 15 2021.
• Citações Web of Science: 0

Resumo

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 LNAME, 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. (AU)

• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais
• Beneficiário: Gilberto de Nucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático