title: Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats.
abstract: BACKGROUND
  Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established.
  
  
  OBJECTIVE
  Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function.
  
  
  METHODS
  Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated.
  
  
  METHODS
  Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used.
  
  
  CONCLUSIONS
  CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0mg/kg increased micturition intervals and volumes by 52% (p<0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively. Cannabinor 0.3 or 1.0mg/kg or vehicle did not affect urodynamic parameters.
  
  
  CONCLUSIONS
  Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on "afferent" urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited.
authors.affiliation: Department of Clinical and Experimental Pharmacology, Lund University, 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: Thomas R
authors.initials: TR
authors.lastname: Downs
authors.forename: Iris
authors.initials: I
authors.lastname: Alroy
authors.forename: Jan S
authors.initials: JS
authors.lastname: Rosenbaum
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D011984:Sensory Receptor Cells / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000187:drug effects*; D014563:Urodynamics / Q000187:drug effects*; D019459:Urothelium / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*
chemical_list: D002186:Cannabinoids; C469526:Cnr2 protein, rat; D043885:Receptor, Cannabinoid, CB2; C555879:cannabinor