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Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist.
Br J Pharmacol 2005; 146(7):917-26BJ

Abstract

Delta9-tetrahydrocannabivarin (THCV) displaced [(3)H]CP55940 from specific binding sites on mouse brain and CHO-hCB(2) cell membranes (K(i)=75.4 and 62.8 nM, respectively).THCV (1 microM) also antagonized CP55940-induced stimulation of [(35)S]GTPgammaS binding to these membranes (apparent K(B)=93.1 and 10.1 nM, respectively). In the mouse vas deferens, the ability of Delta9-tetrahydrocannabinol (THC) to inhibit electrically evoked contractions was antagonized by THCV, its apparent K(B)-value (96.7 nM) approximating the apparent K(B)-values for its antagonism of CP55940- and R-(+)-WIN55212-induced stimulation of [(35)S]GTPgammaS binding to mouse brain membranes. THCV also antagonized R-(+)-WIN55212, anandamide, methanandamide and CP55940 in the vas deferens, but with lower apparent K(B)-values (1.5, 1.2, 4.6 and 10.3 nM, respectively).THCV (100 nM) did not oppose clonidine, capsaicin or (-)-7-hydroxy-cannabidiol-dimethylheptyl-induced inhibition of electrically evoked contractions of the vas deferens. Contractile responses of the vas deferens to phenylephrine hydrochloride or beta,gamma-methylene-ATP were not reduced by 1microM THCV or R-(+)-WIN55212, suggesting that THCV interacts with R-(+)-WIN55212 at prejunctional sites. At 32 microM, THCV did reduce contractile responses to phenylephrine hydrochloride and beta,gamma-methylene-ATP, and above 3 microM it inhibited electrically evoked contractions of the vas deferens in an SR141716A-independent manner. In conclusion, THCV behaves as a competitive CB(1) and CB(2) 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.

Authors+Show Affiliations

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16205722

Citation

Thomas, Adèle, et al. "Evidence That the Plant Cannabinoid Delta9-tetrahydrocannabivarin Is a Cannabinoid CB1 and CB2 Receptor Antagonist." British Journal of Pharmacology, vol. 146, no. 7, 2005, pp. 917-26.
Thomas A, Stevenson LA, Wease KN, et al. Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br J Pharmacol. 2005;146(7):917-26.
Thomas, A., Stevenson, L. A., Wease, K. N., Price, M. R., Baillie, G., Ross, R. A., & Pertwee, R. G. (2005). Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. British Journal of Pharmacology, 146(7), pp. 917-26.
Thomas A, et al. Evidence That the Plant Cannabinoid Delta9-tetrahydrocannabivarin Is a Cannabinoid CB1 and CB2 Receptor Antagonist. Br J Pharmacol. 2005;146(7):917-26. PubMed PMID: 16205722.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. AU - Thomas,Adèle, AU - Stevenson,Lesley A, AU - Wease,Kerrie N, AU - Price,Martin R, AU - Baillie,Gemma, AU - Ross,Ruth A, AU - Pertwee,Roger G, PY - 2005/10/6/pubmed PY - 2006/1/21/medline PY - 2005/10/6/entrez SP - 917 EP - 26 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 146 IS - 7 N2 - Delta9-tetrahydrocannabivarin (THCV) displaced [(3)H]CP55940 from specific binding sites on mouse brain and CHO-hCB(2) cell membranes (K(i)=75.4 and 62.8 nM, respectively).THCV (1 microM) also antagonized CP55940-induced stimulation of [(35)S]GTPgammaS binding to these membranes (apparent K(B)=93.1 and 10.1 nM, respectively). In the mouse vas deferens, the ability of Delta9-tetrahydrocannabinol (THC) to inhibit electrically evoked contractions was antagonized by THCV, its apparent K(B)-value (96.7 nM) approximating the apparent K(B)-values for its antagonism of CP55940- and R-(+)-WIN55212-induced stimulation of [(35)S]GTPgammaS binding to mouse brain membranes. THCV also antagonized R-(+)-WIN55212, anandamide, methanandamide and CP55940 in the vas deferens, but with lower apparent K(B)-values (1.5, 1.2, 4.6 and 10.3 nM, respectively).THCV (100 nM) did not oppose clonidine, capsaicin or (-)-7-hydroxy-cannabidiol-dimethylheptyl-induced inhibition of electrically evoked contractions of the vas deferens. Contractile responses of the vas deferens to phenylephrine hydrochloride or beta,gamma-methylene-ATP were not reduced by 1microM THCV or R-(+)-WIN55212, suggesting that THCV interacts with R-(+)-WIN55212 at prejunctional sites. At 32 microM, THCV did reduce contractile responses to phenylephrine hydrochloride and beta,gamma-methylene-ATP, and above 3 microM it inhibited electrically evoked contractions of the vas deferens in an SR141716A-independent manner. In conclusion, THCV behaves as a competitive CB(1) and CB(2) 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/16205722/Evidence_that_the_plant_cannabinoid_Delta9_tetrahydrocannabivarin_is_a_cannabinoid_CB1_and_CB2_receptor_antagonist_ L2 - https://doi.org/10.1038/sj.bjp.0706414 DB - PRIME DP - Unbound Medicine ER -