Abstract
Although the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.
Key Points
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The urothelium, a specialized lining of the urinary tract, has historically been viewed as a passive barrier to ions and solutes
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There is evidence that the urothelium responds to both physiological and chemical stimuli and can release a number of signaling molecules
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Release of chemical mediators from urothelial cells indicates that these cells have specialized sensory and signaling properties that could allow reciprocal communication with neighboring urothelial cells, as well as afferent and efferent nerves or other cells (i.e. myofibroblasts and immune or inflammatory cells) within the bladder wall
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Various types of transient receptor potential channels including TRPV1 are expressed in the urothelium as well as in bladder afferent nerves
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Results from TRPV1-null mice demonstrate that TRPV1 receptors are essential for normal mechanically evoked purinergic signaling by the urothelium, and indicate that the function of these receptors extends beyond pain sensation to include participation in normal bladder function
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Acknowledgements
This work was supported by NIH grants to L Birder (RO1 DK54824 and RO1 DK57284).
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Lori Birder has associations with the following companies: Hydra Biosciences Inc., Roche Palo Alto LLC, Dynogen Pharmaceuticals Inc., Pfizer Inc., and Omeros Corporation.
William C de Groat has associations with the following companies: Abbott Laboratories, Roche Palo Alto LLC, Eli Lilly and Company, Pfizer Inc., Novartis AG, Dynogen Pharmaceuticals Inc., Johnson & Johnson, Lilly ICOS LLC, Astellas Pharma Inc., Hydra Biosciences Inc., Boehringer Ingleheim, Allergan Inc. and Sanofi Aventis.
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Birder, L., de Groat, W. Mechanisms of Disease: involvement of the urothelium in bladder dysfunction. Nat Rev Urol 4, 46–54 (2007). https://doi.org/10.1038/ncpuro0672
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DOI: https://doi.org/10.1038/ncpuro0672
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