title: Suppression of bladder overactivity by adenosine A2A receptor antagonist in a rat model of Parkinson disease.
abstract: OBJECTIVE
  Overactive bladder is highly prevalent among patients with Parkinson disease. Adenosine is an important neurotransmitter in the central nervous system but it is not fully clarified how adenosine receptors regulate the micturition reflex. Thus, we examined the effect of an adenosine A2A receptor antagonist on the micturition reflex in a rat model of Parkinson disease.
  
  
  METHODS
  In a rat model of Parkinson disease induced by 6-hydroxydopamine (Tocris Bioscience, Ellisville, Missouri) injection we examined the effects of the adenosine A2A receptor antagonist ZM241385, the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole on bladder activity.
  
  
  RESULTS
  Intravenous administration of ZM241385 increased the intercontraction interval in a dose dependent manner in rats with Parkinson disease and sham operated rats but the inhibitory effect was greater in the Parkinson disease group. Intrathecal and intracerebroventricular administration of ZM241385 increased the intercontraction interval in each group. However, in rats with Parkinson disease the inhibitory effects induced by intracerebroventricular administration of ZM241385 were greater than in sham operated rats. Intravenous administration of SKF38393 increased the intercontraction interval in rats with Parkinson disease and subsequent administration of ZM further increased the intercontraction interval. However, SKF38393 did not increase the intercontraction interval after ZM241385 application. Also, ZM241385 increased the intercontraction interval without being affected by pre-administration or post-administration of quinpirole, which decreased the intercontraction interval.
  
  
  CONCLUSIONS
  Results indicate that the adenosine A2A receptor mediated excitatory mechanism is enhanced at a supraspinal site to induce bladder overactivity and A2A receptor inhibition effectively suppresses bladder overactivity in rats with Parkinson disease. Thus, adenosine A2A receptor antagonists could be useful for bladder dysfunction in Parkinson disease cases.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Takeya
authors.initials: T
authors.lastname: Kitta
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Sadako
authors.initials: S
authors.lastname: Kuno
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D010300:Parkinson Disease / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385