British journal of pharmacology · 2026
A role for epithelium-derived 6-nitrodopamine on human ureter contractility.
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Neto Wilmar Azal, Oliveira Denis Lima, Britto-Júnior José, Miller Alex Henrique, Lorenzon Flaviano, Jacintho Felipe Fernandes, de Souza Valéria Barbosa, Mariano Fernanda Viviane, Schenka André Almeida, Mónica Fabiola Zakia, Fregonesi Adriano, Antunes Edson, De Nucci Gilberto
Аннотация
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°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.
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°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.