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A role for epithelium-derived 6-nitrodopamine on human ureter contractility

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Neto, Wilmar Azal ; Oliveira, Denis Lima ; Britto-Junior, Jose ; Miller, Alex Henrique ; Lorenzon, Flaviano ; Jacintho, Felipe Fernandes ; de Souza, Valeria Barbosa ; Mariano, Fernanda Viviane ; Schenka, Andre Almeida ; Monica, Fabiola Zakia ; Fregonesi, Adriano ; Antunes, Edson ; de Nucci, Gilberto
Total Authors: 13
Document type: Journal article
Source: British Journal of Pharmacology; v. N/A, p. 16-pg., 2026-01-07.
Abstract

Background and Purpose To investigate the basal release of 6-nitrodopamine (6-ND) from human isolated ureter and the role of this novel catecholamine in the ureter contractility.Experimental Approach Ureters from 67 brain-dead organ donors (40 males and 27 females) were used during kidney transplantation procedures. After retrieval, a 2-cm distal ureter segment was isolated and incubated in Krebs-Henseleit solution at 37 degrees C with continuous oxygenation. Basal 6-ND release was measured using liquid chromatography-tandem mass spectrometry. Studies were performed on 5-mm ureter rings mounted in tissue baths with isometric tension recorded via PowerLab system. Tyrosine hydroxylase (TH), S100, Pgp9.5 and eNOS expression were analysed using immunohistochemistry and fluorescence in situ hybridization (FISH).Key Results The basal release of 6-ND was significantly reduced in epithelium-denuded compared with intact-epithelium samples. 6-ND induced concentration-dependent contractions of human ureter rings (pEC50 5.3 +/- 0.2). In addition, 6-ND at 10 and 100 nM significantly potentiated contractions induced by noradrenaline and at 1 and 10 nM by adrenaline. TH was detected in epithelial cells of all human ureter samples (n = 5), with moderate to strong positivity. TH expression was confirmed by FISH. S100 and Pgp9.5 immunostaining revealed distinct patterns of nerve fibres in the tunica media and adventitia, while eNOS and TH were both expressed in the mucosal epithelium, with eNOS mainly at the surface and TH towards the basal layer.Conclusions and Implications The finding that 6-ND is released by human ureter and modulates ureter smooth muscle contractility offers a novel insight on ureteral peristalsis mechanisms. (AU)

FAPESP's process: 23/04217-6 - A reappraisal of the regulatory role of the endothelium over the cardiovascular system from a comparative perspective
Grantee:Gilberto de Nucci
Support Opportunities: Research Grants - Visiting Researcher Grant - International
FAPESP's process: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
Grantee:Gilberto de Nucci
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 24/08067-1 - Assessment of the stability of new endogenous catecholamines in biological liquids and identification of possible metabolites
Grantee:Alex Henrique Miller
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 23/13692-0 - In vitro and in vivo evaluation of nitrated derivatives of propranolol and atenolol
Grantee:Flaviano Lorenzon
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system
Grantee:José Britto Júnior
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 21/13726-6 - Identification of molecules related to the synthesis of adrenaline, noradrenaline and dopamine in the endothelium of reptiles and mammals by immunohistochemistry and in situ hibridization
Grantee:Valéria Barbosa de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 23/16075-1 - Characterization of the 6-ND receptor through in vitro evaluation of nitrated analogues of propranolol and atenolol without positive chronotropic effects induced by 6-nitrodopamine, dopamine, noradrenaline and adrenaline.
Grantee:Denis Lima Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 24/10306-4 - Methylglyoxal - advanced glycation end products (AGEs) - receptor for AGEs (AGEr) axis: A potential therapeutical target for prevention and treatment of bladder dysfunction associated with obesity and diabetes
Grantee:Edson Antunes
Support Opportunities: Regular Research Grants