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Inhibition of Peripheral FAAH Depresses Activities of Bladder Mechanosensitive Nerve Fibers of the Rat
University of Tokyo, Japan.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
University of Munich, Germany.
University of Tokyo, Japan.
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2014 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, no 3, 956-963 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: FAAH degrades endocannabinoids and fatty acid amides. FAAH inhibition reduces micturition frequency and counteracts bladder overactivity in rats. We studied the effects of the peripherally active selective FAAH inhibitor URB937, and the CB1 and CB2 receptor antagonists rimonabant and SR144528, respectively, on single unit afferent activity of primary bladder afferents in rats. Materials and Methods: Female Sprague Dawley (R) rats were anesthetized. Single unit afferent activity of A delta or C-fibers from the L6 dorsal roots was recorded during bladder filling before and after URB937 administration with or without rimonabant or SR144528. Drugs (1 mg/kg) were given intravenously. FAAH, CB1 and CB2 expression, and expression of the sensory marker CGRP in the L6 dorsal root ganglion were compared by immunofluorescence. Results: A total of 102 single afferent fibers (48 A delta and 54 C-fibers) were isolated from 57 rats. URB937 decreased single unit afferent activity of C-fibers to a mean +/- SEM of 78% +/- 9% and of A delta-fibers to a mean of 67% +/- 7% while increasing bladder compliance to a mean of 116% +/- 3%. The effects of URB937 on single unit afferent activity and bladder compliance were counteracted by rimonabant or SR144528. Rimonabant increased single unit afferent activity of each fiber type but SR144528 affected only A delta-fiber activity. CGRP positive L6 dorsal root ganglion neurons showed strong FAAH, CB1 and CB2 staining. Conclusions: To our knowledge we report for the first time that inhibiting peripheral FAAH depresses the Ad and C-fiber activity of primary bladder afferents via CB1 and CB2 receptors. CB antagonists alone exerted facilitatory effects on single unit afferent activity during bladder filling in rats. The endocannabinoid system may be involved in physiological control of micturition as regulators of afferent signals.

Place, publisher, year, edition, pages
Elsevier , 2014. Vol. 192, no 3, 956-963 p.
Keyword [en]
urinary bladder; endocannabinoids; nerves, afferent; urination; receptors, cannabinoid
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-111459DOI: 10.1016/j.juro.2014.04.008ISI: 000342105600110PubMedID: 24746881OAI: diva2:757211

Funding Agencies|Ministry of Education, Culture, Sport, Science and Technology of the Japanese Government [40159588, 80595257]; Shimabara Science Promotion Foundation, Tokyo, Japan; Gester Foundation, Helsingborg, Sweden

Available from: 2014-10-21 Created: 2014-10-17 Last updated: 2014-10-21

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