Evidence for an urethro-vesical crosstalk mediated by serotonin

To study the contribution of urethral serotonin for the urethro-vesical crosstalk METHODS: Urethane-anesthetized female rats and TPH1^-/- mice underwent isovolumetric or urethral-opened cystometries during intravesical or intraurethral infusion of saline or serotonin solutions. Human and rat bladders and urethrae were immunoreacted against serotonin and neuronal markers. Serotonin concentration and TPH1 mRNA were determined in rat tissue by HPLC and qPCR.

In rats, under isovolumetric conditions, intraurethral serotonin infusion, but not saline, evoked bladder contractions. This was abolished by urethral anesthesia and by treatment with serotonin receptor antagonists. Serotonin infusion into the bladder had no effect. Under urethral-opened conditions, serotonin infusion reduced the frequency and increased the amplitude of reflex voiding contractions, compared to saline infusion. TPH1^-/- mice, under urethral-opened conditions, exhibited increased frequency and reduced amplitude of voiding contractions compared to WT. Serotonin concentration and TPH1 mRNA expression were higher in the urethra than in the bladder. Cells 5-HT⁺ were found in the human and rat urethral epithelium, close to a sub-epithelial network of cholinergic and sensory fibers, but not in the bladder.

Serotonin, produced and released by urethral cells activates an urethro-vesical pathway that enhances bladder reflex contractions.