Development of novel pharmacological treatment of lower urinary tract dysfunction by targeting bladder afferent transduction

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To find out novel therapeutic targets for bladder storage dysfunction, such as overactive bladder and hypersensitive bladder, or voiding dysfunction due to detrusor underactivity, we evaluated the mechanisms of action of antimuscarimnics, alpha1-adreonceptor (AR) antagonists, beta3-AR agonists and PDE-5 inhibitors to inhibit bladder mechanosensory afferent activities in the rat, and analyzed changes in receptors and ion channels in pathological animal models or bladder mucosa taken from patients with interstitial cystitis. The results suggest that TRPM2, A1, V4, N-type and t-type Ca2+ channels, and FAAH are promising novel targets for these bladder dysfuntions.