title: Cannabinor, a selective cannabinoid-2 receptor agonist, improves bladder emptying in rats with partial urethral obstruction.
abstract: OBJECTIVE
  We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle.
  
  
  METHODS
  A total of 24 female Sprague-Dawley® rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies.
  
  
  RESULTS
  Mean ± SEM bladder weight was 0.97 ± 0.15 gm in controls and 0.53 ± 0.08 gm in cannabinor treated rats (p <0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 ± 0.07 and 0.06 ± 0.02 ml, mean micturition compliance was 0.032 ± 0.006 and 0.069 ± 0.016 ml/cm H(2)O, and mean bladder wall force at the start of flow was 950 ± 280 and 1,647 ± 325 mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma®) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips.
  
  
  CONCLUSIONS
  In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction.
authors.affiliation: Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.forename: Tomi
authors.initials: T
authors.lastname: Streng
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Iris
authors.initials: I
authors.lastname: Alroy
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Limberg
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Downs
authors.forename: Jan S
authors.initials: JS
authors.lastname: Rosenbaum
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D002187:Cannabinol / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D012016:Reference Values; D016896:Treatment Outcome; D014524:Urethral Obstruction / Q000188:drug therapy*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D001745:Urinary Bladder Diseases / Q000188:drug therapy*; D014554:Urination / Q000187:drug effects
chemical_list: D043885:Receptor, Cannabinoid, CB2; D002187:Cannabinol