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From urgency to frequency: facts and controversies of TRPs in the lower urinary tract

Abstract

The members of transient receptor potential (TRP) superfamily of cationic ion channels represent universal sensors, which convert multiple exogenous and endogenous chemical and physical stimuli into electrical and functional cellular responses. TRPs are widely distributed in many different tissues, and expression of numerous TRP types has been reported in lower urinary tract (LUT) tissues, neuronal fibers innervating the bladder and urethra, and epithelial and muscular layers of the bladder and urethral walls, where they are mainly involved in nociception and mechanosensory transduction. As such, they represent attractive targets for treating LUT disorders. Although information on the functional significance of many of the TRP proteins in the LUT remains very limited, compelling evidence has accumulated for a pivotal role of TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 in normal and pathological LUT function, mainly as sensors of stretch and chemical irritation. Further studies into these and other TRPs in the LUT will facilitate the development of improved therapeutic strategies to target these channels in LUT disorders.

Key Points

  • Several members of the transient receptor potential (TRP) superfamily of ion channels are expressed in the lower urinary tract (LUT) and are implicated in LUT function, mainly as sensors of stretch or chemical irritation

  • TRPV4 is the principal urothelial mechanosensor activated by bladder distention and modulates the micturition reflex via a urothelial mechanosensory signaling pathway

  • Cold and menthol-activated TRPM8 in bladder afferents mediates the bladder cooling reflex and is involved in the pathophysiology of idiopathic detrusor overactivity and painful bladder syndrome

  • TRPA1 is a sensor of endogenous and environmental irritants and proalgesic agents in bladder afferents, mediating the effects of inflammatory mediators in the LUT via afferent-type and efferent-type sensory signaling

  • The only clinical targeting of TRPs in LUT disorders has been pharmacological desensitization of the capsaicin receptor TRPV1 with intravesical vanilloids for symptomatic treatment of neurogenic detrusor overactivity via suppression of bladder afferent hyperexcitability

  • The expression and function of these TRPs in other LUT tissues remains controversial, and further studies are necessary to understand the roles of LUT TRPs and develop therapeutic strategies involving these channels

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Figure 1: Cross-sectional layers of bladder wall and the associated expression of TRPs.

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Acknowledgements

The research of N. Prevarskaya and R. Skryma is supported by grants from INSERM (Institut National de la Santé et de la Recherche Médicale), Ligue Nationale Contre le Cancer, FRM (Fondation de Recherche Medicale), ARC (Association pour la Recherche sur le Cancer) and Région Nord/Pas-de-Calais. The research of Y. Shuba is supported by targeted NASU programs “Genome” and “Key laboratory”. Y. Shuba is also supported by the visiting scientist program of Université de Lille.

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Skryma, R., Prevarskaya, N., Gkika, D. et al. From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. Nat Rev Urol 8, 617–630 (2011). https://doi.org/10.1038/nrurol.2011.142

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