title: Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats.
abstract: OBJECTIVE
  This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder. Cannabinoid receptor (CBR) activity may be involved in the regulation of bladder function. However, the role of CBR subtypes in micturition has yet to be established. CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant.
  
  
  METHODS
  Cystometry under urethane anaesthesia was performed to evaluate the effect of intravesical delivery of CP55,940 with or without administration of CB1 antagonist AM251 or CB2 antagonist AM630 on bladder function in female rats. The effects of CP55,940 were also examined in rats with urinary irritation induced by intravesical infusion of acetic acid.
  
  
  RESULTS
  Infusion of CP55,940 significantly (p < 0.05) increased micturition interval (MI) and bladder capacity (BC) by 52 % and decreased maximal voiding pressure (MP) by 25 %. Pretreatment with AM251 or AM630 before CP55,940 administration prevented CP55,940-induced increases in MI, BC and reduced MP. Acetic acid induced urinary frequency as evidenced by a reduction in MI and was suppressed by CP55,940.
  
  
  CONCLUSIONS
  CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.
authors.affiliation: Department of Health Sciences, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, University of Leicester, PO Box 65, Leicester, LE2 7LX, UK. evibakali@me.com.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Bakali
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Mbaki
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Lambert
authors.affiliation: Department of Health Sciences, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, University of Leicester, PO Box 65, Leicester, LE2 7LX, UK.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Elliott
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Mason
authors.affiliation: Department of Health Sciences, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, University of Leicester, PO Box 65, Leicester, LE2 7LX, UK.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Tincello
mesh_terms: D019342:Acetic Acid; D000283:Administration, Intravesical; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007211:Indoles / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D019342:Acetic Acid; C094023:iodopravadoline
keywords: Cannabinoid receptors; Cystometry; Overactive bladder; Urinary bladder