Giorgio Gandaglia and Frank Strittmatter contributed equally to the manuscript.
The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats
Article first published online: 29 AUG 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 33, Issue 8, pages 1251–1258, November 2014
How to Cite
Gandaglia, G., Strittmatter, F., La Croce, G., Benigni, F., Bettiga, A., Castiglione, F., Moschini, M., Mistretta, F., Gratzke, C., Montorsi, F., Stief, C. and Hedlund, P. (2014), The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats. Neurourol. Urodyn., 33: 1251–1258. doi: 10.1002/nau.22482
Christopher Chapple led the peer-review process as the Associate Editor responsible for the paper.
Conflict of interest: none.
- Issue published online: 13 OCT 2014
- Article first published online: 29 AUG 2013
- Manuscript Accepted: 19 JUL 2013
- Manuscript Received: 15 MAY 2013
- cannabinoid receptor;
- endocannabinoid system;
- mitogen-activated protein kinase;
- urinary bladder
To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).
Sprague–Dawley rats received daily subcutaneous injections of OEtA (0.3 mg/kg), or vehicle for 2 weeks. Cystometries, organ bath studies, Western blot, and immunofluorescence were then used. Expressions of FAAH, cannabinoid 1 and 2 receptors (CB1 and CB2), mitogen-activated protein kinase (MAPK), vesicular acetyl choline-transporter protein (VAChT), and calcitonin gene-related peptide (CGRP) were evaluated.
At baseline, OEtA-treated rats had higher values (P < 0.05) of micturition intervals (MI) and volumes (MV), bladder capacity (BC), threshold pressure, and flow pressure than vehicle controls. Intravesical PGE2 reduced MI, MV, and BC, and increased basal pressure and the area under the curve in all rats. However, these urodynamic parameters were altered less by intravesical PGE2 in OEtA-treated rats (P < 0.05 vs. vehicle controls). Compared to vehicle controls, detrusor from OEtA-treated rats had larger contractions to carbachol at 10–0.1 µM, but no difference in Emax was recorded. FAAH, CB1, CB2, VAChT, or CGRP was similarly expressed in bladders from all rats. In separate experiments, intravesical OEtA increased mucosal expression of phosphorylated MAPK.
Chronic FAAH inhibition altered sensory urodynamic parameters and reduced bladder overactivity. Even if it cannot be excluded that OEtA may act on central nervous sensory pathways to contribute to these effects, the presence of FAAH and CB receptors in the bladder and activation of intracellular signals for CB receptors by intravesical OEtA suggest a local role for FAAH in micturition control. Neurourol. Urodynam. 33:1251–1258, 2014. © 2013 Wiley Periodicals, Inc.