Evidence that (-)-7-hydroxy-4′-dimethylheptyl-cannabidiol activates a non-CB1, non-CB2, non-TRPV1 target in the mouse vas deferens

Roger G. Pertwee*, Adèle Thomas, Lesley A. Stevenson, Yehoshua Maor, Raphael Mechoulam

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Previous experiments showed that R-(+)-WIN55212-induced inhibition of electrically-evoked contractions of mouse vasa deferentia could be antagonized by cannabidiol in a manner that appeared to be competitive but not to involve direct competition for established cannabinoid receptors. We have now discovered that (-)-7-hydroxy-4′-dimethylheptyl-cannabidiol (7-OH-DMH-CBD) inhibits electrically-evoked contractions of the vas deferens (EC50 = 13.3 nM). This it appeared to do by acting on prejunctional neurones as 100 nM 7-OH-DMH-CBD did not attenuate contractile responses to phenylephrine or β,γ-methylene-ATP. Although 7-OH-DMH-CBD was antagonized by SR141716A, it was less susceptible to antagonism by this CB1 receptor antagonist than R-(+)-WIN55212. 7-OH-DMH-CBD was also antagonized by cannabidiol (1 μM; apparent KB = 222.2 nM) but not by the CB 2 receptor antagonist, SR144528 (32 nM), or by naloxone (300 nM), ruthenium red (1 μM) or capsazepine (10 μM). Yohimbine (100 nM) enhanced the ability of 7-OH-DMH-CBD to inhibit electrically-evoked contractions. R-(+)-WIN55212 was also potentiated by 100 nM yohimbine, possibly reflecting ongoing sequestration of Gi/o proteins from CB1 receptors by α2-adrenoceptors. Our results suggest that 7-OH-DMH-CBD may activate a neuronal target in the vas deferens that is not a CB1, CB2, TRPV1, opioid or α2-adrenergic receptor but do not exclude the possibility that it also activates CB1 receptors.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalNeuropharmacology
Volume48
Issue number8 SPEC. ISS.
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

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Keywords

  • (-)-7-hydroxy-4′-dimethylheptyl-cannabidiol (7-OH-DMH-CBD)
  • Cannabidiol
  • G protein sequestration
  • Mouse vas deferens
  • R-(+)-WIN55212
  • Yohimbine

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