The pivotal role of neuronal nitric oxide synthase in the release of 6-nitrodopamine from mouse isolated vas deferens

被引:4
作者
Britto-Junior, Jose [1 ,7 ]
Silva, Samuel Goulart Nacario [1 ]
Lima, Antonio Tiago [1 ]
Fuguhara, Vivian [1 ]
Andrade, Larissa Bueno [1 ]
Mendes, Gustavo Duarte [2 ,3 ]
Peterson, Larryn W. [4 ]
Chiavegatto, Silvana [5 ,6 ]
Antunes, Edson [1 ]
De Nucci, Gilberto [1 ,2 ,3 ,4 ]
机构
[1] Univ Estadual Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas, SP, Brazil
[3] Univ Metropolitana Santos, Fac Med, Dept Pharmacol, Santos, SP, Brazil
[4] Rhodes Coll, Dept Chem, Memphis, TN 38112 USA
[5] Univ Sao Paulo ICB USP, Inst Biomed Sci ICB, Dept Pharmacol, Sao Paulo, Brazil
[6] Univ Sao Paulo Med Sch FMUSP, Inst Psychiat IPq, Dept Psychiat, Sao Paulo, Brazil
[7] Univ Campinas Unicamp, Fac Med Sci, Dept Pharmacol, Rua Tessalia Vieira Camargo,126 Cidade Univ, BR-13083887 Campinas, SP, Brazil
来源
NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2024年 / 143卷
基金
巴西圣保罗研究基金会;
关键词
Liquid chromatography; Tandem mass spectrometry; Dopamine; Noradrenaline; Adrenaline; Catecholamine; NERVE; 6-HYDROXYDOPAMINE; OXIDATION; DOPAMINE;
D O I
10.1016/j.niox.2023.12.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
6-Nitrodopamine (6-ND) is released from rat and human vas deferens and is considered a major mediator of both tissues contractility. The contractions induced by 6-ND are selectively blocked by both tricyclic antidepressants and alpha 1-adrenoceptor antagonists. Endothelial nitric oxide synthase (eNOS) is the major isoform responsible for 6ND release in mouse isolated heart, however the origin of 6-ND in the vas deferens is unknown. Here it was investigated by LC-MS/MS the basal release of 6-ND from isolated vas deferens obtained from control, eNOS-/-, nNOS-/-, and iNOS- /- mice. In addition, it was evaluated in vitro vas deferens contractility following electric field stimulation (EFS).Basal release of 6-ND was significantly reduced in nNOS-/- mice compared to control mice, but not decreased when the vas deferens were obtained from either eNOS-/- or iNOS-/- mice. Pre-incubation of the vas deferens with tetrodotoxin (1 mu M) significantly reduced the basal release of 6-ND from control, eNOS- /-, and iNOS-/mice but had no effect on the basal release of 6-ND from nNOS-/- mice. EFS-induced frequency-dependent contractions of the vas deferens, which were significantly reduced when the tissues obtained from control, eNOS-/- and iNOS- /- mice, were pre-incubated with L-NAME, but unaltered when the vas deferens was obtained from nNOS-/- mice. In addition, the EFS-induced contractions were significantly smaller when the vas deferens were obtained from nNOS-/- mice.The results clearly demonstrate that nNOS is the main NO isoform responsible for 6-ND release in mouse vas deferens and reinforces the concept of 6-ND as a major modulator of vas deferens contractility.
引用
收藏
页码:1 / 8
页数:8
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