6-Nitrodopamine is an endogenous mediator of rat isolated epididymal vas deferens contractions induced by electric-field stimulation

Britto-Júnior, José; Ximenes, Luiz; Ribeiro, André; Fregonesi, Adriano; Campos, Rafael; Kiguti, Luiz Ricardo de Almeida; Mónica, Fabíola Z.; Antunes, Edson; Nucci, Gilberto De

doi:10.1016/j.ejphar.2021.174544

Cited by 18 publications

(18 citation statements)

References 52 publications

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“…Chronic treatment of rats with L-NAME also decreases the 6-ND release by vas deferens. 3 However, the effect of L-NAME pretreatment in the human vas deferens has two distinct characteristics of the rat, namely, in the rat vas deferens, although incubation with L-NAME decreased the basal release of 6-ND, it did not affect the contractions induced by EFS, an indication that 6-ND is probably stocked in vesicles in the animal species. Another interesting difference is that in contrast to the rat vas deferens, inhibition of 6-ND in human vas deferens is accompanied by an equivalent increase of dopamine levels.…”

Section: Discussionmentioning

confidence: 99%

“…shown to be released from rat isolated vas deferens 3 and atria 4 and from human umbilical cord vessels. 5 The synthesis/release of 6nitrodopamine is reduced (but not abolished) when these tissues are incubated with the nitric oxide (NO) synthase inhibitor L-NAME.…”

Section: Introductionmentioning

confidence: 97%

“…Since 6-nitrodopamine is a potent vasodilator, 5,7 the formation of this novel catecholamine rather than stimulation of soluble guanlylate cyclase 8 may be an important mechanism of action for NO. The contractions caused by 6-ND in the rat isolated vas deferens are selectively antagonized by tricyclic antidepressants such as amitriptyline, desipramine and clomipramine 3 and by α 1 -adrenergic receptor blockers such as doxazosin, tamsulosin and silodosin. 9 The clinical use of tricyclic antidepressants has been associated with delayed ejaculation, 10 and the tricyclic antidepressant clomipramine has therapeutic indication in the control of premature ejaculation in man.…”

Section: Introductionmentioning

confidence: 99%

“…Contractions of the vas deferens also have an important role in the propulsion of the spermatozoa and occur near‐simultaneously with the contractions of the seminal glands 2 . 6‐nitrodopamine (6‐ND) is a new catecholamine that has been recently shown to be released from rat isolated vas deferens 3 and atria 4 and from human umbilical cord vessels 5 . The synthesis/release of 6‐nitrodopamine is reduced (but not abolished) when these tissues are incubated with the nitric oxide (NO) synthase inhibitor L‐NAME.…”

Section: Introductionmentioning

confidence: 99%

“…Since 6‐nitrodopamine is a potent vasodilator, 5,7 the formation of this novel catecholamine rather than stimulation of soluble guanlylate cyclase 8 may be an important mechanism of action for NO. The contractions caused by 6‐ND in the rat isolated vas deferens are selectively antagonized by tricyclic antidepressants such as amitriptyline, desipramine and clomipramine 3 and by α 1 ‐adrenergic receptor blockers such as doxazosin, tamsulosin and silodosin 9 …”

Section: Introductionmentioning

confidence: 99%

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6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

et al. 2022

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Background Rat isolated vas deferens releases 6‐nitrodopamine (6‐ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the α1‐adrenergic receptors such as doxazosin, tamsulosin, and prazosin. Objectives To investigate the liberation of 6‐ND by human epididymal vas deferens (HEVDs) and its pharmacological actions. Methods The in vitro liberation of 6‐ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC‐MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric‐field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L‐NAME and the release of catecholamines and the contractile response to EFS were assessed. Results 6‐ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6‐ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L‐NAME reduced both the 6‐ND release and the contractions induced by EFS. Discussion and conclusion 6‐ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and α1‐adrenergic receptor antagonists.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

et al. 2022

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Measurement of 6‐cyanodopamine, 6‐nitrodopa, 6‐nitrodopamine and 6‐nitroadrenaline by LC–MS/MS in Krebs–Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles

Júnior,

Britto‐Júnior,

Magalhaes

et al. 2023

Biomedical Chromatography

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This study presents the validation of a sensitive method for the determination of 6‐nitrodopa, 6‐nitrodopamine, 6‐nitroadrenaline and 6‐cyanodopamine in Krebs–Henseleit solution by LC–MS/MS with ESI+. HRMS was used to precisely characterize the structures of the fragment ions. The method was applied to investigate the catecholamine basal release from rabbit isolated atria and ventricles. The atria and ventricles were suspended separately in a 5 ml organ bath containing Krebs–Henseleit solution with ascorbic acid (3 mM), gassed (95%O2/5%CO2) at 37°C for 30 min. Strata‐X 33 μm SPE cartridges were employed for the extraction of the catecholamines and the internal standard 6‐nitrodopamine‐d4. The catecholamines were separated employing a 150 × 3 mm Shim‐pack GIST C18‐AQ (3 mm particle size), placed in an oven at 40°C and perfused by 65% of mobile phase A (MeCN/H2O; 90/10, v/v) + 0.4% CH3COOH and 35% mobile phase B (deionized H2O) + 0.2% CH2O2 at 320 μl/min in isocratic mode. The method was linear at 0.1–20 ng/ml. The method was used to identify for the first‐time basal release of the three nitrocatecholamines mentioned above and a member of a novel class of catecholamines, the cyanocatecholamines.

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β1- and β1/β2-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens

Lima

Amorim

Britto-Júnior

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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6-nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective b-adrenergic receptor antagonists have been associated with ejaculatory failure.Here, the effects of selective b 1 -and b 1/ b 2 -adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline and EFS were investigated. The selective b 1 adrenergic receptor antagonists atenolol (0.1 and 1mM), betaxolol (1mM) and metoprolol (1mM) and the unselective b 1 /b 2 -adrenergic receptor antagonists propranolol (1 and 10mM) and pindolol (10mM) caused signi cant rightward shifts of the concentration-response curve to 6-ND (pA 2 6.41,

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6-Nitrodopamine is an endogenous mediator of rat isolated epididymal vas deferens contractions induced by electric-field stimulation

Cited by 18 publications

References 52 publications

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

Measurement of 6‐cyanodopamine, 6‐nitrodopa, 6‐nitrodopamine and 6‐nitroadrenaline by LC–MS/MS in Krebs–Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles

β1- and β1/β2-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens

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