Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats

Füllhase Claudius, Schreiber Andrea, Giese Armin, Schmidt Michael, Montorsi Francesco, Gratzke Christian, La Croce Giovanni, Castiglione Fabio, Stief Christian, Hedlund Petter

Research output: Contribution to journalArticle

Abstract

Aims: 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) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5μg rimonabant (CB1 antagonist) or 5μg 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.

Original languageEnglish
JournalNeurourology and Urodynamics
DOIs
Publication statusAccepted/In press - 2015

Keywords

  • AM251
  • Bladder
  • Endocannabinoid
  • Obstruction
  • Oleoyl ethyl amide
  • Overactivity
  • Rimonabant
  • SR144528

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

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    Claudius, F., Andrea, S., Armin, G., Michael, S., Francesco, M., Christian, G., Giovanni, L. C., Fabio, C., Christian, S., & Petter, H. (Accepted/In press). Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats. Neurourology and Urodynamics. https://doi.org/10.1002/nau.22753