Evidence for an urethro‐vesical crosstalk mediated by serotonin

Abstract

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

Underactive bladder in aging rats is associated with a reduced number of serotonin‐expressing cells in the urethra and is improved by serotonin application to the urethra

“…Although it could be argued that normalization of BVE could have resulted from an action of 5‐HT on the bladder itself because the instillations were performed through the bladder dome, this is unlikely. In fact, in a recent study it was shown that 5‐HT solution instilled only in the bladder of female rats or mice had no detectable effect on bladder contractility; improvements in bladder contractions were only observed when 5‐HT was applied to the urethra, where it stimulated 5‐HT 2 and 5‐HT 3 receptors …”

“…Briefly, rats were anesthetized with urethane (1.2 g/kg body weight) and body temperature was kept constant using a temperature controller (WPI ATC 1000 DC, World Precision Instruments Inc, FL, USA). The bladder was exposed through a midline incision in the lower abdomen, and saline was infused through the bladder dome at a rate of 6 mL/h, using a WPI SP100IZ syringe pump (World Precision Instruments Inc, FL, USA) . The frequency and amplitude of bladder contractions was recorded after a 30‐minute stabilization period (WPI labtrax 4/16 with WPI Transbridge TBM 4 M) (World Precision Instruments Inc, FL, USA).…”

“…Already recognized mechanisms underlying DU include degeneration of bladder smooth muscle cells, disorders affecting central nervous system control of the voiding reflex, and disruption of the efferent–afferent nerves of the lower urinary tract . A less explored mechanism is modification of the urethra–bladder reflex . Urethral anesthesia with lidocaine inhibits subepithelial afferent nerves and prevents the occurrence of effective bladder contractions in humans and other mammals .…”

“…Recent studies showed that the sensory information necessary to initiate the urethral bladder reflex is at least partially generated by cross‐talk between specialized neuronal‐like urethral cells expressing serotonin (5‐hydroxytryptamine [5‐HT]) and the underlying sensory fibers . Stimulation of rat urethra by 5‐HT activates lumbosacral spinal cord neurons in segments where bladder motor nerves are located, and enhances detrusor contractions, even at low volumes of bladder filling . These 5‐HT‐induced effects were mediated by excitation of urethral sensory fibers because they were abolished by local anesthesia with 2% lidocaine …”

“…Stimulation of rat urethra by 5‐HT activates lumbosacral spinal cord neurons in segments where bladder motor nerves are located, and enhances detrusor contractions, even at low volumes of bladder filling . These 5‐HT‐induced effects were mediated by excitation of urethral sensory fibers because they were abolished by local anesthesia with 2% lidocaine …”