ROLE OF 6-NITRODOPAMINE IN MOTILITY OF ISOLATED RABBIT URETER

• Grant number: 25/00804-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Alan Vitor Farias Linhares
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines, AP.TEM

Abstract

The aim of this project is to investigate the role of 6-nitrodopamine (6-ND) in the motility of isolated rabbit ureters, analyzing its basal release and physiological effects in comparison with classical catecholamines, such as dopamine, noradrenaline and adrenaline. 6-ND was initially identified in different vascular tissues and organs, including the aorta of several species, as well as the heart of rabbits and mice, where its release depends on the activity of the enzyme nitric oxide synthase (NOS). This substance has demonstrated vasorelaxant action in previously contracted vessels, and its interaction with catecholamines suggests a significant regulatory role.In addition to vascular tissues, studies show that 6-ND also has modulatory effects on the contraction of non-vascular tissues, such as the seminal vesicle and bladder, which raises the hypothesis that it may influence the motility of other systems. This project aims to compare the responses of isolated rabbit ureters to 6-ND with those induced by other catecholamines, evaluate the interaction with adrenergic receptors, and investigate the effects of adenylate cyclase antagonists and inhibitors.The release of 6-ND will be quantified by liquid chromatography coupled to mass spectrometry (LC-MS/MS), while the influence of the epithelium and innervation will be explored through immunohistochemistry and in situ hybridization analyses. In addition, the study will examine the dynamics of 6-ND release in different regions of the ureter, investigating its modulation of contractile effects and the impact of factors such as epithelial removal and the use of inhibitors.With this, the project aims to expand the understanding of 6-ND as a potential motility modulator, exploring its possible therapeutic applications in urinary tract dysfunctions.