Abstract
1. Delta(9)-tetrahydrocannabivarin (THCV) displaced [H-3]CP55940 from specific binding sites on mouse brain and CHO-hCB(2) cell membranes (K-i = 75.4 and 62.8 nm, respectively).
2 THCV (1 mu M) also antagonized CP55940-incluced stimulation of [S-35]GTP S binding to these membranes (apparent K-B = 93.1 and 10.1 nM, respectively).
3 In the mouse vas deferens, the ability of Delta(9)-tetrahydrocannabinol (THC) to inhibit electrically evoked contractions was antagonized by THCV, its apparent K-B-value (96.7nm) approximating the apparent K-B-values for its antagonism of CP55940- and R-(+)-WIN55212-induced stimulation of [S-35]GTP gamma S binding to mouse brain membranes.
4 THCV also antagonized R-(+)-WIN55212, anandamide, methanandamide and CP55940 in the vas deferens, but with lower apparent KB-values (1.5, 1.2, 4.6 and 10.3 nm, respectively).
5 THCV (100nm) did not oppose clonidine, capsaicin or (-)-7-liydroxy-cannabidiol-dimethylheptyl-induced inhibition of electrically evoked contractions of the vas deferens.
6 Contractile responses of the vas deferens to phenylephrine hydrochloride or beta,gamma-methylene-ATP were not reduced by 1 mu m THCV or R-(+)-WIN55212, suggesting that THCV interacts with R-(+)WIN55212 at prejunctional sites.
7 At 32 mu m, THCV did reduce contractile responses to phenylephrine hydrochloride and beta,gamma-methylene-ATP, and above 3 pm it inhibited electrically evoked contractions of the vas deferens in an SR141716A-independent manner.
8 In conclusion, THCV behaves as a competitive CB1 and CB2 receptor antagonist. In the vas deferens, it antagonized several cannabinoids more potently than THC and was also more potent against CP55940 and R-(+)-WIN55212 in this tissue than in brain membranes. The bases of these agonist- and tissue-dependent effects remain to be established.
Original language | English |
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Pages (from-to) | 917-926 |
Number of pages | 9 |
Journal | British Journal of Pharmacology |
Volume | 146 |
Issue number | 7 |
DOIs | |
Publication status | Published - Dec 2005 |
Keywords
- Delta(9)-tetrahydrocannabivarin
- Delta(9)-tetrahydrocannabinol
- R-(+)-WIN55212
- anandamide
- methanandamide
- CP55940
- cannabinoids
- mouse vas deferens
- CB1 receptor antagonist
- CB2 receptor antagonist
- nonadrenaline release
- selective antagonist
- inverse agonism
- nervous-system
- pharmacology
- acetylcholine
- modulation
- non-CB1
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Cannabis as a source of medicines
Roger Pertwee (Coordinator), P Consroe (Coordinator), R Musty (Coordinator) & David Baker (Coordinator)
Impact: Health and Wellbeing