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 language | English |
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Pages (from-to) | 1139-1146 |
Number of pages | 8 |
Journal | Neuropharmacology |
Volume | 48 |
Issue number | 8 SPEC. ISS. |
DOIs | |
Publication status | Published - Jun 2005 |
Externally published | Yes |
Keywords
- (-)-7-hydroxy-4′-dimethylheptyl-cannabidiol (7-OH-DMH-CBD)
- Cannabidiol
- G protein sequestration
- Mouse vas deferens
- R-(+)-WIN55212
- Yohimbine