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

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

Life Sci

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.

Published: July 2024

AI Article Synopsis

  • The study aimed to evaluate the release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles and understand its effects and sources.
  • Using organ baths and advanced testing methods like LC-MS/MS, researchers found that 6-ND was released in higher amounts compared to other catecholamines and was not affected by sodium channel blockers.
  • The findings suggest that 6-ND, originating from the epithelial cells of the seminal vesicles, plays a significant role in enhancing the contraction of smooth muscle by amplifying the effects of noradrenaline.

Article Abstract

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:5%CO) 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 and E 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 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 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.

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Source
http://dx.doi.org/10.1016/j.lfs.2024.122695DOI Listing

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