In the urinary bladder, the capsaicin-gated ion channel TRPV1 is expressed both within afferent nerve terminals and within the epithelial cells that line the bladder lumen. To determine the significance of this expression pattern, we analyzed bladder function in mice lacking TRPV1. Compared with wild-type littermates, trpv1−/− mice had a higher frequency of low-amplitude, non-voiding bladder contractions. This alteration was accompanied by reductions in both spinal cord signaling and reflex voiding during bladder filling (under anesthesia). In vitro, stretch-evoked ATP release and membrane capacitance changes were diminished in bladders excised from trpv1−/− mice, as was hypoosmolality-evoked ATP release from cultured trpv1−/− urothelial cells. These findings indicate that TRPV1 participates in normal bladder function and is essential for normal mechanically evoked purinergic signaling by the urothelium.
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This work was supported by NIH grants R01 DK54824 and R01 DK57284 (to L.A.B.), R01 DK54425 (to G.A.), R01 HL57985 (to A.J.K.) and by grants from The American Cancer Society (RSG-01-063-01-CSM) and the Blaustein Pain Research Fund (to M.J.C.). We thank R.T. Evans and J. Wang for expert technical assistance, W. Shaner for assistance with graphics, K. Gabrielson for assistance with pathology and C.A. Maggi for his critical comments.
M. J. Caterina is an inventor on a patent for the use of the TRPV1 cDNA.
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Birder, L., Nakamura, Y., Kiss, S. et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5, 856–860 (2002). https://doi.org/10.1038/nn902
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