The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

被引:93
作者
Bolognini, Daniele [2 ,3 ]
Costa, Barbara [4 ]
Maione, Sabatino [5 ]
Comelli, Francesca [4 ]
Marini, Pietro
Di Marzo, Vincenzo [6 ]
Parolaro, Daniela [2 ,3 ]
Ross, Ruth A.
Gauson, Lisa A.
Cascio, Maria G.
Pertwee, Roger G. [1 ]
机构
[1] Univ Aberdeen, Sch Med Sci, Inst Med Sci, Aberdeen AB2S 2ZD, Scotland
[2] Univ Insubria, DBSF, Pharmacol Sect, Varese, Italy
[3] Univ Insubria, Ctr Neurosci, Varese, Italy
[4] Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy
[5] Univ Naples 2, Endocannabinoid Res Grp, Div Pharmacol L Donatelli, Dept Expt Med, Naples, Italy
[6] CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80125 Naples, Italy
基金
美国国家卫生研究院;
关键词
Delta; 9-Tetrahydrocannabivarin; CP55940; CB(2) receptor; CB(1) receptor; pertussis toxin; pain; inflammation; carrageenan; formalin; CB2; RECEPTOR; AGONIST; DELTA(9)-TETRAHYDROCANNABIVARIN; PHARMACOLOGY; MORPHINE; INVERSE; NEURONS; CANNABIDIOL; STIMULATION; TRAFFICKING;
D O I
10.1111/j.1476-5381.2010.00756.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and purpose: The phytocannabinoid, Delta 9-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders. Experimental approach: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [35S]GTP gamma S binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist. Key results: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50) = 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng center dot mL-1) and stimulated [35S]GTP gamma S binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg center dot kg-1 i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg center dot kg-1, and in both phases of this test at 5 mg center dot kg-1; these effects of THCV appeared to be CB(1) and CB(2) receptor mediated. Conclusions and implications: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x.
引用
收藏
页码:677 / 687
页数:11
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