6-Nitrodopamine as a Novel Mediator of Prostatic Smooth Muscle Function in Mouse and Human.

BACKGROUND: Epithelium-derived catecholamines contribute to local regulation of genitourinary smooth muscle function, but the role of the endogenous 6-nitrodopamine (6-ND) in the prostate remains unknown. OBJECTIVES: To determine whether 6-ND is produced by mouse and human prostate and its role in smooth muscle regulation. METHODS: Catecholamine release was quantified by LC-MS/MS. Tyrosine hydroxylase (TH) expression was assessed by immunohistochemistry and FISH. Functional responses were evaluated by myography and void spot assay. RESULTS: Basal 6-ND release was detected in mouse and human prostate. In mice, release was partially sensitive to tetrodotoxin (TTX), whereas in human tissues it was largely TTX-resistant. TH expression was identified in the prostatic epithelium. Functionally, 6-ND relaxed pre-contracted tissues, attenuated neurogenic contractions, and reduced noradrenaline potency. Genetic deletion of nitric oxide synthases (e/i/nNOS-/-) or inhibition was associated with prostatic hypercontractility and reduced voiding frequency. Although 6-ND-induced relaxation was independent of the NO-sGC-cGMP pathway and did not increase intracellular cAMP, it potentiated forskolin-induced relaxation. DISCUSSION: These findings identify 6-ND as an endogenous modulator of prostatic smooth muscle function and are consistent with a dual regulatory system integrating neuronal and epithelial catecholamine sources. CONCLUSION: 6-ND represents a novel pathway involved in local prostate regulation and a potential therapeutic target for prostatic disorders.