Functional and Molecular Characterization of Hyposensitive Underactive Bladder Tissue and Urine in Streptozotocin-Induced Diabetic Rat
OBJECTIVES To investigate the effect of intrathecal administration of E-series prostaglandin 1 antagonist in cyclophosphamide-induced murine cystitis. METHODS Female Wistar rats were used for this experimental study. Intrathecal administration of E-series prostaglandin 1 antagonist (ONO-8711; 0.5, 5 and 50 µg) in sham controls and rats with cystitis induced by a single intraperitoneal injection of cyclophosphamide (300 mg/kg) was assessed by evaluating micturition pressure and intercontraction interval using a conscious-filling cystometry at 48 h after cyclophosphamide or saline injection. In both groups, prostaglandin E2 concentrations and the expression of E-series prostaglandin 1 receptor in the spinal cord were measured by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. RESULTS Rats with cyclophosphamide-induced cystitis showed a shorter intercontraction interval compared with controls, where the cumulative intrathecal administration of ONO-8711 did not significantly change micturition pressure or intercontraction interval compared with the baseline. In rats with cyclophosphamide-induced cystitis, each dose of ONO-8711 significantly increased the intercontraction interval compared with the baseline (46% increase at 50 µg intrathecally). Polymerase chain reaction revealed the expression of E-series prostaglandin 1 receptor in the spinal cord of both sham and cyclophosphamide-induced cystitis rats. In rats with cyclophosphamide-induced cystitis, PGE2 concentration in the dorsal horn of the L5-6 spinal cord was significantly higher than that in controls (3.55 ± 1.24 vs 0.99 ± 0.06 pg/mg tissue). CONCLUSIONS In rats with cyclophosphamide-induced cystitis, urinary frequency seems to be caused by prostaglandin E2 acting on E-series prostaglandin 1 receptor at the level of the spinal cord. Blockade of the spinal E-series prostaglandin 1 receptor by ONO-8711 might have a therapeutic potential in the control of interstitial cystitis/bladder pain syndrome.