Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2−/− and P2X3−/− mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex.

Takezawa K, Kondo M, Kiuchi H, Soda T, Takao T, Miyagawa Y, Tsujimura A, Nonomura N, Shimada S. Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis. Am J Physiol Renal Physiol 307: F234 -F241, 2014. First published May 7, 2014 doi:10.1152/ajprenal.00043.2014.-Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction. bladder ultrasonography; cystometry; mouse; LPS; cystitis VARIOUS DISEASES CAUSE BLADDER dysfunction with lower urinary tract symptoms (11). Some diseases, such as overactive bladder, interstitial cystitis, and neurogenic bladder, lead to storage failure, and other diseases, such as underactive bladder and bladder neck construction, lead to voiding failure. Objective evaluation of bladder function is indispensable for accurate diagnosis and development of appropriate treatment strategy for these diseases. Bladder ultrasonography, which can evaluate postvoiding residual volume and bladder wall thickness, is noninvasive and the most common examination for bladder function (5). Cystometry, which can identify detrusor overactivity, low bladder compliance (BCP), and sensory urgency, is an invasive but gold standard examination for bladder function (8). Thus these ex...

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Background The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement. Methods We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate‐enlargement (PE) group; those with prostate volumes <30 ml were defined as the non‐PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups. Results The PE group included 66 patients; the non‐PE group included 62 patients. Age, body mass index, and prostate‐specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non‐PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non‐PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015). Conclusion The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.

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This work was supported by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JP16K20133). The authors declare no competing interests.

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Recently, conflicting evidence has led us to question the role of urothelial ATP signaling in normal micturition reflex. In contrast, under pathological conditions, it seems likely that enhanced urothelial ATP signaling mediates bladder hyperactivity. These recent findings suggest that the urothelial ATP signaling pathway is a potential therapeutic target for bladder functional disorders.