title: Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats.
abstract: OBJECTIVE
  To test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors.
  
  
  METHODS
  Male rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3 mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5 μg rimonabant (CB1 antagonist) or 5 μg SR144528 (CB2 antagonist) were studied in awake rats.
  
  
  RESULTS
  After administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH.
  
  
  CONCLUSIONS
  Urodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. © 2015 Wiley Periodicals, Inc.
authors: Department of Urology, University of Rostock, Rostock, Germany.|Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany.
authors: Claudius
authors: C
authors: Füllhase
authors: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany.|Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
authors: Andrea
authors: A
authors: Schreiber
authors: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany.
authors: Armin
authors: A
authors: Giese
authors: Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
authors: Michael
authors: M
authors: Schmidt
authors: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.|Universita Vita San Raffaele, Milan, Italy.
authors: Francesco
authors: F
authors: Montorsi
authors: Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
authors: Christian
authors: C
authors: Gratzke
authors: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
authors: Giovanni
authors: G
authors: La Croce
authors: Universita Vita San Raffaele, Milan, Italy.|Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
authors: Fabio
authors: F
authors: Castiglione
authors: Department of Urology, Ludwig-Maximilians-University, Munich, Germany.
authors: Christian
authors: C
authors: Stief
authors: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Clinical Pharmacology, Linköping University, Linköping, Sweden.
authors: Petter
authors: P
authors: Hedlund
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001892:Camphanes; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C110630:SR 144528; C571010:oleoyl ethyl amide; C103505:AM 251
keywords: AM251; SR144528; bladder; endocannabinoid; obstruction; oleoyl ethyl amide; overactivity; rimonabant