Introduction

Urothelial ATP signaling has been believed to have an essential role in micturition reflex. To clarify the exact role of urothelial ATP signaling in micturition reflex, we performed detailed in vivo functional analyses in purinergic receptor-deficient mice (Takezawa et al., Sci Rep, 2016).

Methods

Male C57BL/6J mice, P2X₂^-/-, and P2X₃^-/- mice were used. For the bladder functional analyses, the voided volume per micturition of free-moving mice was assessed by automated voided stain on paper method (Negoro et al., Nat commun, 2012), and the bladder capacity, post-voiding residual volume and intercontraction intervals were evaluated by mouse video-urodynamics testing (Takezawa et al., Am J Physiol Renal Physiol, 2014). (1) Bladder function under normal conditions was examined in wild-type (WT), P2X₂^-/-, and P2X₃^-/- mice. (2) Lipopolysaccharide (LPS)-induced changes of bladder function and increases in c-Fos-positive cells in the L6 spinal cord were analyzed in WT, P2X₂^-/-, and P2X₃^-/- mice.

Results

(1) Unexpectedly, a lack of P2X₂ or P2X₃ receptors did not affect bladder function under normal conditions (Figure 1). (2) In contrast, the LPS-induced bladder hyperactivity and an increase in c-Fos-positive cells in the L6 spinal cord were attenuated in P2X₂^-/-, and P2X₃^-/- mice (Figure 2).

Conclusions

These findings indicate that urothelial ATP signaling is not essential for normal micturition reflex under physiological conditions, but plays an important role in bladder hyperactivity under pathological conditions.

Funding

none