Epithelium-derived catecholamines and modulation of respiratory smooth muscle contractility cells and inflammatory cells

• Grant number: 25/00926-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Flaviano Lorenzon
• Supervisor: Simon Charles Pitchford
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: King's College London, England
• Associated to the scholarship: 23/13692-0 - In vitro and in vivo evaluation of nitrated derivatives of propranolol and atenolol, BP.PD

Abstract

The respiratory system, critical for homeostasis, is influenced by both neuronal and non-neuronal mechanisms regulating airway smooth muscle tone. Traditional paradigms emphasize the adrenergic nervous system and catecholamine release from nerve terminals. However, recent discoveries challenge this view, highlighting the role of non-neuronal catecholamines, including endothelium-derived molecules like 6-nitrodopamine (6-ND). Preliminary data indicates the presence of 6-ND in respiratory epithelial cells, suggesting an autocrine or paracrine role in modulating airway smooth muscle reactivity and inflammatory processes. This study aims to elucidate the role of 6-ND in respiratory physiology. Using human airway cell lines, we will investigate tyrosine hydroxylase expression, basal release of catecholamines, and intracellular signaling pathways modulated by 6-ND. Advanced techniques such as immunohistochemistry, fluorescence in situ hybridization, and liquid chromatography-mass spectrometry will be employed. We will also assess the interaction of 6-ND with classical catecholamines and its potential effects on intracellular calcium and cAMP levels. The findings could provide novel insights into airway physiology, challenging existing paradigms and unveiling new therapeutic targets for asthma, chronic obstructive pulmonary disease, and other respiratory conditions. (AU)