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

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2022-10, Vol.260, p.109403-109403, Article 109403
• Main Authors: Britto-Júnior, José, Campos, Rafael, Peixoto, Matheus, Lima, Antonio Tiago, Jacintho, Felipe Fernandes, Mónica, Fabíola Z., Moreno, Ronilson Agnaldo, Antunes, Edson, De Nucci, Gilberto
• Format: Article
• Language: English
• Subjects: Dopamine; Endothelium; Nitric oxide; Nitrocatecholamines; Vascular smooth muscle
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2022.109403

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 μM) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 μM) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA2 6.09) and L-NAME pre-treated endothelium-intact (pA2 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 μM). In the thromboxane A2 mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM–1 μM) and the dopamine D2-receptor antagonist haloperidol (1 nM-1 μM) 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 D2-like receptor antagonist. [Display omitted] •6-ND caused a rightward shift of the concentration-response curves to dopamine but did not affect the responses of noradrenaline and adrenaline.•6-ND is suggestibly acting as a dopaminergic antagonist, with selectivity for the D2-receptor in Chelonoidis carbonaria aortic rings.