title: Effect of intrathecal administration of E-series prostaglandin 1 receptor antagonist in a cyclophosphamide-induced cystitis rat model.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Renal and Urologic Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. nwada@asahikawa-med.ac.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Wada
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kita
authors.forename: Masaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kazumi
authors.initials: K
authors.lastname: Hashizume
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kakizaki
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000494:pharmacology; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007278:Injections, Spinal; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000037:antagonists & inhibitors*; D012016:Reference Values; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000517:prevention & control*
chemical_list: D001643:Bridged Bicyclo Compounds; D002208:Caproates; C122148:ONO 8711; D058306:Receptors, Prostaglandin E, EP1 Subtype; D003520:Cyclophosphamide