6-Nitrodopamine potentiates contractions of rat isolated vas deferens induced by noradrenaline, adrenaline, dopamine and electric field stimulation

José Britto-Júnior; Antonio Tiago Lima; Rafael Campos; Alexandre Asturiano Gião; Gustavo Duarte Mendes; Luiza P Ferreira-Novaes Silva; Adriano Fregonesi; André Sampaio Pupo; Edson Antunes; Gilberto De Nucci

doi:10.1007/s00210-023-02478-6

6-Nitrodopamine potentiates contractions of rat isolated vas deferens induced by noradrenaline, adrenaline, dopamine and electric field stimulation

Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct;396(10):2555-2570. doi: 10.1007/s00210-023-02478-6. Epub 2023 Apr 4.

Affiliations

¹ Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil. josebrittojr@dac.unicamp.br.
² Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
³ Faculty of Medicine, São Leopoldo Mandic (SLMANDIC), Campinas, SP, Brazil.
⁴ Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Brazil.
⁵ Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.

PMID: 37014401
DOI: 10.1007/s00210-023-02478-6

Abstract

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, α₁ and β₁β₂ 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_2A-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.

Keywords: Atropine; Indomethacin; Nitrocatecholamines; Reserpine; Synergism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catecholamines / pharmacology
Dopamine / pharmacology
Electric Stimulation
Epinephrine / pharmacology
Idazoxan / pharmacology
Male
Muscle Contraction
Norepinephrine* / pharmacology
Rats
Receptors, Adrenergic
Vas Deferens*

Substances

Norepinephrine
Epinephrine
6-nitrodopamine
Dopamine
Idazoxan
Catecholamines
Receptors, Adrenergic