| Texto completo | |
| Autor(es): |
Britto-Junior, Jose
;
Luvizotto, Rodrigo
;
Jabbour, Sami
;
Lima, Antonio Tiago
;
Miller, Alex Henrique
;
Moraes, Maria Elisabete A.
;
Peterson, Larryn W.
;
Antunes, Edson
;
Fregonesi, Adriano
;
De Nucci, Gilberto
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | European Journal of Pharmacology; v. 1012, p. 9-pg., 2026-01-20. |
| Resumo | |
6-Cyanodopamine (6-CYD) is a novel endogenous catecholamine that is released from rat isolated vas deferens epithelium and regulates smooth muscle contractility. Here it was investigated whether 6-CYD is released from human epididymal vas deferens (HEVD) and its interaction with the classical catecholamines dopamine, noradrenaline, and adrenaline. Basal release of 6-CYD was quantified by liquid chromatography coupled to tandem mass spectrometry in the absence and presence of either the voltage-gated sodium channel blocker tetrodotoxin or the dual NADPH oxidase NOX1,4 inhibitor GKT137831. Concentration-response curves to dopamine, noradrenaline, and adrenaline were performed in the presence and absence of 6-CYD. Frequencydependent electric-field stimulation (EFS) was conducted with and without pre-incubation with 6-CYD. The basal release of 6-CYD was decreased with pre-incubation with GKT137831 and unaffected by tetrodotoxin. Although 6-CYD itself (up to 100 mu M) did not induce HEVD contractions, at 10 nM it remarkably potentiated the contractions induced by dopamine, noradrenaline, and EFS. At 100 nM, 6-CYD also potentiated the adrenalineinduced HEVD contractions. The potentiation of noradrenaline-induced contractions by 6-CYD was not observed in HEVD pre-treated with tetrodotoxin (1 mu M). In separate experiments, HEVD strips also released 6-nitrodopamine (6-ND) that was significantly reduced by GKT137831 (1 mu M). Co-incubation (30 min) with 6-CYD (100 pM) and 6-ND (100 pM) caused a significant leftward shift in the concentration-response curve to noradrenaline. The results indicate that epithelium 6-CYD is an endogenous mediator of HEVD contractility. Whether NADPH oxidases are involved in 6-CYD biosynthesis remains to be further investigated. (AU) | |
| Processo FAPESP: | 24/10306-4 - Eixo metilglioxal - produtos finais de glicação avançada (AGEs) - receptor para AGEs (AGEr): Potencial alvo terapêutico para prevenção e tratamento da disfunção vesical associada a obesidade e diabetes |
| Beneficiário: | Edson Antunes |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais |
| Beneficiário: | Gilberto de Nucci |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 24/08067-1 - Avaliação da estabilidade de novas catecolaminas endógenas em líquidos biológicos e identificação de possíveis metabólitos |
| Beneficiário: | Alex Henrique Miller |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/14414-8 - Avaliação da ação das nitro-catecolaminas no sistema cardiovascular |
| Beneficiário: | José Britto Júnior |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/13593-6 - Avaliação do tratamento crônico da 6-nitrodopamina em ratos |
| Beneficiário: | Antonio Tiago Silva Lima |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |