Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Faculty of Medicine, São Leopoldo Mandic (SLMANDIC), Campinas, SP, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2555-2570. doi: 10.1007/s00210-023-02478-6. Epub 2023 Apr 4.
6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from the rat isolated vas deferens, and has been characterized as a major modulator of the contractility of rat isolated epididymal vas deferens (RIEVD). Drugs such as tricyclic antidepressants, α and ββ adrenoceptor blockers, act as selective antagonists of the 6-ND receptor in the RIEVD. In the rat isolated atria, 6-ND has a potent positive chronotropic action and causes remarkable potentiation of the positive chronotropic effects induced by dopamine, noradrenaline, and adrenaline. Here, whether 6-ND interacts with the classical catecholamines in the rat isolated vas deferens was investigated. Incubation with 6-ND (0.1 and 1 nM; 30min) caused no contractions in the RIEVD but provoked significant leftward shifts in the concentration-response curves to noradrenaline, adrenaline, and dopamine. Pre-incubation of the RIEVD with 6-ND (1 nM), potentiated the contractions induced by electric-field stimulation (EFS), whereas pre-incubation with 1 nM of dopamine, noradrenaline or adrenaline, did not affect EFS-induced contractions. In tetrodotoxin (1 μM) pre-treated (30 min) RIEVD, pre-incubation with 6-ND (0.1 nM) did not cause leftward shifts in the concentration-dependent contractions induced by noradrenaline, adrenaline, or dopamine. Pre-incubation of the RIEVD with the α-adrenoceptor antagonist idazoxan (30 min, 10 nM) did not affect dopamine, noradrenaline, adrenaline, and EFS-induced contractions. However, when idazoxan (10 nM) and 6-ND (0.1 nM) were simultaneously pre-incubated (30 min), a significant potentiation of the EFS-induced contractions of the RIEVD was observed. 6-nitrodopamine causes remarkable potentiation of dopamine, noradrenaline, and adrenaline contractions on the RIEVD, due to activation of adrenergic terminals, possibly via pre-synaptic adrenoceptors.
6-硝基多巴胺（6-ND）是一种新型内源性儿茶酚胺，从大鼠离体输精管中释放出来，并被描述为大鼠离体附睾输精管（RIEVD）收缩性的主要调节剂。三环类抗抑郁药、α 和β肾上腺素受体阻滞剂等药物在 RIEVD 中作为 6-ND 受体的选择性拮抗剂。在大鼠离体心房中，6-ND 具有很强的正变时作用，并显著增强多巴胺、去甲肾上腺素和肾上腺素诱导的正变时作用。在这里，研究了 6-ND 是否与大鼠离体输精管中的经典儿茶酚胺相互作用。孵育 6-ND（0.1 和 1 nM；30min）不会引起 RIEVD 收缩，但会引起去甲肾上腺素、肾上腺素和多巴胺浓度反应曲线的显著左移。RIEVD 预孵育 6-ND（1 nM）增强了电场刺激（EFS）诱导的收缩，而预孵育 1 nM 多巴胺、去甲肾上腺素或肾上腺素不会影响 EFS 诱导的收缩。在 1 μM 河豚毒素（30 min）预处理的 RIEVD 中，0.1 nM 6-ND 预孵育不会引起去甲肾上腺素、肾上腺素或多巴胺诱导的浓度依赖性收缩的左移。RIEVD 预孵育 30 min，10 nMα-肾上腺素受体拮抗剂伊达唑胺（idazoxan）不会影响多巴胺、去甲肾上腺素、肾上腺素和 EFS 诱导的收缩。然而，当伊达唑胺（10 nM）和 6-ND（0.1 nM）同时预孵育 30 min 时，观察到 RIEVD 的 EFS 诱导收缩显著增强。6-硝基多巴胺通过激活肾上腺素能末梢，可能通过突触前肾上腺素受体，显著增强 RIEVD 上多巴胺、去甲肾上腺素和肾上腺素的收缩作用。
