Epithelium-derived 6-nitrodopamine modulates noradrenaline-induced contractions in human seminal vesicles.

Autor: Britto-Júnior J; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil. Electronic address: josebrittojr@dac.unicamp.br., Uramoto EHS; Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil., Lima AT; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil., Ribeiro LF; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil; Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, Brazil., de Souza VB; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil., Schenka AA; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil., de Almeida Magalhães JC; Metropolitan University of Santos (UNIMES), Santos, Brazil., Antunes E; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil., Fregonesi A; Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil; Division of Urology, Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil., De Nucci G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil; Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Jul 01; Vol. 348, pp. 122695. Date of Electronic Publication: 2024 May 06.
DOI: 10.1016/j.lfs.2024.122695
Abstrakt: Aims: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin.
Main Methods: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O 2 :5%CO 2 ) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC 50 and E max values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH).
Key Findings: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 μM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC 50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10 -8  M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips.
Significance: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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