Modulation of Stretch Evoked Adenosine Triphosphate Release From Bladder Epithelium by Prostaglandin E-2

Purpose: We previously reported that cyclooxygenase inhibitors improved storage function in rats with detrusor overactivity caused by cerebral infarction via C-fiber suppression but the precise mechanism underlying this effect remained unclear. In this study we investigated the effects of cyclooxygenase inhibitors on stretch evoked adenosine triphosphate and prostaglandin E-2 release from bladder epithelium. Materials and Methods: Whole bladders excised from normal rats were fixed vertically in an organ bath filled with Krebs solution. Bladders were infused with 0.3 ml Krebs solution (baseline), followed by 0.9 ml vehicle or 1.5 ml vehicle/drug solution, or 0.3 ml protamine sulfate (Wako Pure Chemical Industries, Osaka, Japan), followed by 0.3 ml prostaglandin E-2 (Nacalai Tesque, Kyoto, Japan). Solutions were allowed to stand for 10 minutes and collected. Adenosine triphosphate and prostaglandin E-2 concentrations were measured by luciferin-luciferase assay and enzyme-linked immunoassay, respectively. Results: Adenosine triphosphate and prostaglandin E-2 release from bladder epithelium was increased by distention in volume dependent fashion. A 100 mu M dose of the nonselective cyclooxygenase inhibitors FYO-750, ketoprofen and indomethacin significantly suppressed the increased adenosine triphosphate and prostaglandin E-2 release. Inhibition of adenosine triphosphate release by 100 mu M FYO-750 and indomethacin was antagonized by prostaglandin E-2 co-injection. Prostaglandin E-2 increased adenosine triphosphate release in a nondistending condition, and the 1 mu M of the selective EP1 and EP3 receptor antagonists ONO-8711 and ONO-AE5-599, respectively, significantly suppressed the increased adenosine triphosphate release. Conclusions: Results indicate that cyclooxygenase inhibitors suppress adenosine triphosphate release from bladder epithelium via decreasing prostaglandin E-2. EP1 and/or EP3 receptors appear to participate in this effect.