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Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
University of Rostock, Germany; University of Munich, Germany.
University of Munich, Germany; University of Munich, Germany.
University of Munich, Germany.
University of Munich, Germany.
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2016 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, no 4, 464-470 p.Article in journal (Refereed) PublishedText
Abstract [en]

AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats. ResultsAfter 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. ConclusionsUrodynamic 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. (c) 2015 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 35, no 4, 464-470 p.
Keyword [en]
AM251; bladder; endocannabinoid; obstruction; oleoyl ethyl amide; overactivity; rimonabant; SR144528
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-128147DOI: 10.1002/nau.22753ISI: 000374304900006PubMedID: 25788026OAI: oai:DiVA.org:liu-128147DiVA: diva2:929689
Note

Funding Agencies|German Research Foundation (DFG) [GR3333/2-1]; Gester Foundation, Sweden

Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2016-05-19

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Hedlund, Petter
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Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Clinical Pharmacology
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