Compound 48/80 causes overactive bladder without altering urothelial permeability in mice

Abstract

The urothelium, a transitional epithelium lining the urinary bladder, is essential for preventing leakage of urine into the underlying tissue. Disruption of this barrier by noxious stimuli or inflammatory mediators increases bladder wall permeability and causes bladder dysfunction. Compound 48/80 is a pro-inflammatory basic secretagogue that causes urothelium-dependent increases in urinary bladder contractility, as well as bladder overactivity in mice. We hypothesized that Compound 48/80 causes bladder dysfunction by increasing urothelial permeability. Intact bladders from male C57BL/6 mice (N=4) were cannulated, filled with HEPES-buffered physiological salt solution containing FITC-labeled-dextran (70 kDa), and pressurized to 25 mmHg. Z-stacks of baseline fluorescence were captured across the bladder wall using 2-photon laser microscopy. Compound 48/80 (50 μg/mL) was then instilled intravesically for 10 minutes before the bladder wall was imaged again. Average FITC intensity plots wall showed no consistent increase in fluorescence with or without Compound 48/80 from the lumen into the bladder wall. There was also no statistical difference in the area under the curve of these line graphs (p=0.5898). Our findings suggest that Compound 48/80 causes overactive bladder without affecting urothelial permeability. Future studies will investigate other secretagogues and lower molecular weight dextrans to clarify the mechanisms by which secretagogues cause a loss of urothelial barrier function. This research is supported by NIH P20-DK127554 (NRT), NIH R01-DK119615 (NRT). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.