(-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens

Roger G. Pertwee*, Ruth A. Ross, Susan J. Craib, Adèle Thomas

*Corresponding author for this work

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The nonpsychoactive plant cannabinoid, (-)-cannabidiol, modulates in vivo responses to Δ9-tetrahydrocannabinol. We have found that cannabidiol can also interact with cannabinoid CB1 receptor agonists in the mouse vas deferens, a tissue in which prejunctional cannabinoid CB1 receptors mediate inhibition of electrically evoked contractions by suppressing noradrenaline and/or ATP release. Cannabidiol (0.316-10 μM) attenuated the ability of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1,4- benzoxazin-6-yl]-1-naphthalenylmethanone (R-(+)-WIN55212) to inhibit contractions in a concentration-related, surmountable manner with a KB value (120.3 nM) well below its reported cannabinoid receptor CB1/CB2 Ki values. Cannabidiol (10 μM) also antagonized (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP55940; KB=34 nM) and [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO; KB=5.6 μM) and attenuated contractile responses to noradrenaline, phenylephrine and methoxamine but not to β, γ-methyleneadenosine 5′-triphosphate. At 3.16-10 μM, it increased the amplitude of evoked contractions, probably by enhancing contractile neurotransmitter release. We conclude that cannabidiol antagonizes R-(+)-WIN55212 and CP55940 by acting at prejunctional sites that are unlikely to be cannabinoid CB1 or CB2 receptors.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalEuropean Journal of Pharmacology
Volume456
Issue number1-3
DOIs
Publication statusPublished - 5 Dec 2002
Externally publishedYes

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Keywords

  • Cannabidiol
  • Cannabinoid CB receptor
  • CP55940
  • Drug interaction
  • Vas deferens, mouse
  • WIN55212

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