title: Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats.
abstract: BACKGROUND
  Cannabinoid receptor (CB)-mediated functions may be involved in the regulation of bladder function, but information on endocannabinoid signals during micturition is scarce.
  
  
  OBJECTIVE
  Investigate the expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human, rat, and mouse bladders and study the effects of inhibition of FAAH during urodynamics in awake rats.
  
  
  METHODS
  Bladder tissue from humans, mice, and rats was used for measurements. Female Sprague-Dawley rats were administered the FAAH inhibitor oleoyl ethyl amide (OEtA) or vehicle intravenously (IV) or intravesically (IVES) with or without rimonabant (CB1 antagonist) or SR144528 (CB2 antagonist).
  
  
  METHODS
  Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats.
  
  
  CONCLUSIONS
  Messenger RNA and protein for FAAH was expressed in the mucosa of human, mouse, and rat urinary bladders. Immunoreactivities for FAAH and CB2 were codistributed in rat and human urothelium. IV OEtA (0.3mg/kg) to rats increased intercontraction intervals (ICIs), micturition volume (MV), bladder capacity (BC), and threshold pressure (TP) by 17±1%, 16±1%, 17±1%, and 19±5%, respectively (all p<0.05 vs baseline). IVES OEtA (1 and 10mg/l) in rats dose-dependently increased (p<0.05 vs baseline) ICI (19±2% and 35±5%), MV (15±3% and 32±4%), BC (16±2% and 34±4%), and TP (15±1%, 21±3%). SR144528 (IVES 5mg/l) abolished all effects of OEtA, whereas rimonabant only counteracted effects of OEtA on TP.
  
  
  CONCLUSIONS
  Bladder mucosa of all species expressed FAAH. Rat and human urothelium coexpressed FAAH and CB2. The FAAH inhibitor OEtA altered urodynamic parameters that reflect sensory functions of micturition in rats. Suggesting a role for the endocannabinoid system in bladder mechanoafferent functions of rats, effects of IVES OEtA were abolished by an IVES CB2 antagonist and partly counteracted by an IVES CB1 antagonist.
authors.affiliation: Department of Urology, Munich University, Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Strittmatter
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.forename: Fabio
authors.initials: F
authors.lastname: Benigni
authors.forename: Arianna
authors.initials: A
authors.lastname: Bettiga
authors.forename: Patrizio
authors.initials: P
authors.lastname: Rigatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.forename: Christian
authors.initials: C
authors.lastname: Stief
authors.forename: Giorgia
authors.initials: G
authors.lastname: Colciago
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000581:Amidohydrolases / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001892:Camphanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects / Q000201:enzymology; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects*; D019459:Urothelium / Q000187:drug effects / Q000201:enzymology; D014851:Wakefulness; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001892:Camphanes; D004791:Enzyme Inhibitors; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C469526:Cnr2 protein, rat; C110630:SR 144528; C571010:oleoyl ethyl amide