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.
| Language | English |
|---|---|
| Pages | 99-106 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 456 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - 5 Dec 2002 |
| Externally published | Yes |
Fingerprint
Keywords
- Cannabidiol
- Cannabinoid CB receptor
- CP55940
- Drug interaction
- Vas deferens, mouse
- WIN55212
Cite this
}
(-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. / Pertwee, Roger G.; Ross, Ruth A.; Craib, Susan J.; Thomas, Adèle.
In: European Journal of Pharmacology, Vol. 456, No. 1-3, 05.12.2002, p. 99-106.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens
AU - Pertwee, Roger G.
AU - Ross, Ruth A.
AU - Craib, Susan J.
AU - Thomas, Adèle
PY - 2002/12/5
Y1 - 2002/12/5
N2 - 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.
AB - 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.
KW - Cannabidiol
KW - Cannabinoid CB receptor
KW - CP55940
KW - Drug interaction
KW - Vas deferens, mouse
KW - WIN55212
UR - http://www.scopus.com/inward/record.url?scp=0037027935&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(02)02624-9
DO - 10.1016/S0014-2999(02)02624-9
M3 - Article
VL - 456
SP - 99
EP - 106
JO - European Journal of Pharmacology
T2 - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -