Evaluation of the release and function of the new catecholamine 6-nitrodopa in the vas deferens

• Grant number: 24/20651-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Maria Clara Carvalho Ramos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Catecholamines act as neurotransmitters and play an important role in the physiology of ejaculation. Recently, the basal release of new catecholamines from the endothelium of vascular tissues in reptiles and mammals, and from the epithelium of the human seminal vesicle and vas deferens, was identified using mass spectrometry. Among these catecholamines, 6-nitrodopamine (6-ND) and 6-cyanedopamine (6-CNDA) stand out. 6-ND has mainly cardiovascular functions, as well as having a significant vasodilatory and positive chronotropic effect that is a hundred times more powerful than adrenaline and noradrenaline in rat atria. It is also capable of promoting contraction of the human vas deferens and potentiating contractions mediated by traditional catecholamines in this tissue, and is considered the main endogenous modulator of vas deferens contraction in humans. 6-CNDA also plays an important role in modulating contraction of the vas deferens, mainly by potentiating noradrenaline-mediated contractions. Like 6-ND and 6-CNDA, basal release of 6-nitrodopa has also been observed in isolated rabbit hearts, but there is no information on the pharmacological action of this new endogenous catecholamine. Therefore, the general aim of this project is to verify whether 6-nitrodopa is released from human and rat vas deferens, and whether it has any pharmacological action in rat vas deferens. To this end, isolated rat vas deferens will be mounted in organ baths and incubated with 6-nitrodopa to assess whether it produces contractile activity in the ductus deferens, with and without induction by electric field stimulation. In addition, the potentiating effect of this new catecholamine on vas deferens contraction mediated by traditional catecholamines (dopamine, noradrenaline and adrenaline) will be evaluated. Finally, we will investigate whether 6-nitrodopa is synergistic with 6-nitrodopamine in this contractile activity.