6-Nitrodopamine potentiates catecholamine-induced contractions of human isolated vas deferens

Abstract

6-Nitrodopamine (6-ND) is the main catecholamine released from human isolated vas deferens and the adrenergic nervous system is known to play a major role in the contractions of the epididymal portion of the vas deferens. Here it was investigated the interactions of 6-ND on the contractions of the human isolated vas deferens induced by either classical catecholamines or electric-field stimulation (EFS). The vas deferens obtained from 106 patients who underwent vasectomy surgery were mounted in a 10-mL glass chamber filled with warmed (37°C) and oxygenated Krebs–Henseleit's solution. The strips were pretreated (30 min) with 6-ND (0.1–100 nM) and exposed to increasing concentrations of noradrenaline (0.01–300 M), dopamine (0.00001–10 mM), or adrenaline (0.01–300 M). The strips were also submitted to EFS in tissues pre-incubated or not with 6-ND (1–100 nM), noradrenaline (100 nM), adrenaline (100 nM), or dopamine (100 nM). Catecholamine basal release was evaluated by LC–MS/MS and expression of tyrosine hydroxylase by both immunohistochemistry (IC) and fluorescence in-situ hybridization (FISH). Pre-incubation of the vas deferens with 6-ND caused marked potentiation of the contractions induced by noradrenaline, adrenaline, and dopamine, as characterized by significant increases in E_max, without changes in pEC₅₀ values. 6-nitrodopamine also caused significant increases in the EFS-induced contractions. The basal release of 6-ND was not affected by pre-treatment of the tissues with tetrodotoxin. Tyrosine hydroxylase was detected in epithelial cells of human vas deferens samples by both IC and FISH. The results clearly demonstrate that epithelium-derived 6-ND is a major modulator of human vas deferens contractility.