| Full text | |
| Author(s): |
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
Total Authors: 10
|
| Document type: | Journal article |
| Source: | European Journal of Pharmacology; v. 1012, p. 9-pg., 2026-01-20. |
| Abstract | |
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) | |
| FAPESP's process: | 24/10306-4 - Methylglyoxal - advanced glycation end products (AGEs) - receptor for AGEs (AGEr) axis: A potential therapeutical target for prevention and treatment of bladder dysfunction associated with obesity and diabetes |
| Grantee: | Edson Antunes |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines |
| Grantee: | Gilberto de Nucci |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 24/08067-1 - Assessment of the stability of new endogenous catecholamines in biological liquids and identification of possible metabolites |
| Grantee: | Alex Henrique Miller |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system |
| Grantee: | José Britto Júnior |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats |
| Grantee: | Antonio Tiago Silva Lima |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |