6-nitrodopamine is a major endogenous modulator of human vas deferens contractility.
Adrenergic Antagonists
/ pharmacology
Amitriptyline
/ pharmacology
Animals
Antidepressive Agents, Tricyclic
/ pharmacology
Carbamazepine
/ pharmacology
Chromatography, Liquid
Desipramine
/ pharmacology
Dopamine
/ analogs & derivatives
Doxazosin
/ pharmacology
Epinephrine
/ pharmacology
Humans
Male
Muscle Contraction
Muscle, Smooth
NG-Nitroarginine Methyl Ester
/ pharmacology
Nitric Oxide
Norepinephrine
/ pharmacology
Prazosin
/ pharmacology
Rats
Receptors, Adrenergic
Tamsulosin
/ pharmacology
Tandem Mass Spectrometry
Vas Deferens
ejaculation
nitric oxide
tricyclic antidepressants
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
revised:
30
07
2022
received:
17
06
2022
accepted:
04
08
2022
pubmed:
9
8
2022
medline:
19
10
2022
entrez:
8
8
2022
Statut:
ppublish
Résumé
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 α To investigate the liberation of 6-ND by human epididymal vas deferens (HEVDs) and its pharmacological actions. 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. 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. 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 α
Sections du résumé
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 α
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 α
Substances chimiques
6-nitrodopamine
0
Adrenergic Antagonists
0
Antidepressive Agents, Tricyclic
0
Receptors, Adrenergic
0
Amitriptyline
1806D8D52K
Nitric Oxide
31C4KY9ESH
Carbamazepine
33CM23913M
Tamsulosin
G3P28OML5I
Doxazosin
NW1291F1W8
Desipramine
TG537D343B
NG-Nitroarginine Methyl Ester
V55S2QJN2X
Dopamine
VTD58H1Z2X
Norepinephrine
X4W3ENH1CV
Prazosin
XM03YJ541D
Epinephrine
YKH834O4BH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1540-1547Informations de copyright
© 2022 American Society of Andrology and European Academy of Andrology.
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