6-Nitrodopamine is an endogenous selective dopamine receptor antagonist in Chelonoidis carbonaria aorta

Autor(es)

Britto-Junior, Jose ; Campos, Rafael ; Peixoto, Matheus ; Lima, Antonio Tiago ; Jacintho, Felipe Fernandes ; Monica, Fabiola Z. ; Moreno, Ronilson Agnaldo ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 260, p. 7-pg., 2022-07-07.

Resumo

Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 mu M) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 mu M) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA(2) 6.09) and L-NAME pre-treated endothelium-intact (pA(2) 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 mu M). In the thromboxane A(2) mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 mu M) and the dopamine D-2-receptor antagonist haloperidol (1 nM-1 mu M) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D-2-like receptor antagonist. (AU)

• 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: 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: 18/24971-9 - Relevância fisiológica das catecolaminas produzidas pelo endotélio
• Beneficiário: Felipe Fernandes Jacintho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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