Basic scienceDetrusor overactivity induced by intravesical application of adenosine 5′-triphosphate under different delivery conditions in rats
Section snippets
Animals
Female Sprague-Dawley rats (weighing 170 to 240 g) were used. The protocol for this study complied with the Guide for the Care and Use of Laboratory Animals, published by the National Institute of Laboratory Animal Resources, and was approved by the University of Pittsburgh Institutional Animal Care and Use Committee.
Cystometry
Under halothane anesthesia, a PE-10 polyethylene catheter (Clay Adams, Parsippany, NJ) was inserted into the right jugular vein, and the free end of the catheter was tunneled
Effect of Intravesical ATP Adjusted to pH 6.0
PBS (pH 6.0) alone when infused into the bladder did not alter any cystometric parameters. Similarly, application of ATP solutions (20 to 60 mM), adjusted to pH 6.0, did not elicit significant detrusor overactivity (Table I).
Effect of ATP (pH 6.0) After PS Infusion
When PS was infused intravesically, bladder overactivity was observed, as evidenced by decreased ICIs (Fig. 1A). After PS infusion, PBS (pH 6.0) was infused intravesically, which partially normalized the cystometric parameters. Intravesical instillation of ATP (20, 40, and
Comment
The bladder permeability barrier is located in the apical membrane of the superficial layer of epithelial cells, so-called umbrella cells.10 Intravesical application of PS has been used to induce bladder epithelial injury,9 which permeabilizes the apical membranes of the urothelium.9 Acetate, propionate, butyrate, or succinate salts at pH 4.4, but not at pH 5.0, alters the transepithelial permeability of the rabbit urothelium.11 In our study, ATP (pH 6.0) alone did not induce significant
Conclusions
Intravesically applied ATP in pH 6.0 solution does not penetrate the intact bladder epithelial layer in the rat because of permeability barrier and ecto-ATPase of the urothelium. Therefore, increased permeability of the bladder epithelium is needed for exogenously applied ATP to activate subepithelial P2X receptors to sensitize C-fiber afferents and induce detrusor overactivity.
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This work was supported by NIH DK68557, DK55045, and DK66138, and the Fishbein Family CURE-IC.