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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.

Strittmatter, Frank; Gandaglia, Giorgio; Benigni, Fabio; Bettiga, Arianna; Rigatti, Patrizio; Montorsi, Francesco; Gratzke, Christian; Stief, Christian; Colciago, Giorgia and Hedlund, Petter LU (2012) In European Urology 61. p.98-106
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. DESIGN, SETTING, AND PARTICIPANTS: 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). MEASUREMENTS:... (More)
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. DESIGN, SETTING, AND PARTICIPANTS: 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). MEASUREMENTS: Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats. RESULTS AND LIMITATIONS: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Urology
volume
61
pages
98 - 106
publisher
Elsevier
external identifiers
  • WOS:000297861800020
  • PMID:21930339
  • Scopus:82255162759
ISSN
1873-7560
DOI
10.1016/j.eururo.2011.09.002
language
English
LU publication?
yes
id
5364a7e9-b53d-4e0b-9c00-e253a415840b (old id 2168759)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21930339?dopt=Abstract
date added to LUP
2011-10-03 11:37:23
date last changed
2016-11-13 04:28:48
@misc{5364a7e9-b53d-4e0b-9c00-e253a415840b,
  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. DESIGN, SETTING, AND PARTICIPANTS: 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). MEASUREMENTS: Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats. RESULTS AND LIMITATIONS: 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&lt;0.05 vs baseline). IVES OEtA (1 and 10mg/l) in rats dose-dependently increased (p&lt;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.},
  author       = {Strittmatter, Frank and Gandaglia, Giorgio and Benigni, Fabio and Bettiga, Arianna and Rigatti, Patrizio and Montorsi, Francesco and Gratzke, Christian and Stief, Christian and Colciago, Giorgia and Hedlund, Petter},
  issn         = {1873-7560},
  language     = {eng},
  pages        = {98--106},
  publisher    = {ARRAY(0xc6a2d48)},
  series       = {European Urology},
  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.},
  url          = {http://dx.doi.org/10.1016/j.eururo.2011.09.002},
  volume       = {61},
  year         = {2012},
}