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Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist
被引:158
作者:
Cascio, M. G.
[1
]
Gauson, L. A.
[1
]
Stevenson, L. A.
[1
]
Ross, R. A.
[1
]
Pertwee, R. G.
[1
]
机构:
[1] Univ Aberdeen, Sch Med Sci, Inst Med Sci, Aberdeen AB25 2ZD, Scotland
基金:
美国国家卫生研究院;
关键词:
cannabigerol;
CP55940;
mouse vas deferens;
alpha(2)-adrenoceptor;
5-HT1A receptor;
CB1;
receptor;
clonidine;
dexmedetomidine;
maprotiline;
R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin;
MOUSE VAS-DEFERENS;
PHARMACOLOGICAL PROFILE;
CB1;
NORADRENALINE;
HASHISH;
RELEASE;
DELTA(9)-TETRAHYDROCANNABIVARIN;
ADRENOCEPTORS;
CONSTITUENTS;
CANNABIDIOL;
D O I:
10.1111/j.1476-5381.2009.00515.x
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Background and purpose: Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Delta(9)-tetrahydrocannabinol, cannabidiol and Delta(9)-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [S-35]GTP gamma S binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [H-3]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent alpha(2)-adrenoceptor agonist (EC50 = 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent K-B = 51.9 nM). At 10 mu M, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be alpha(2)-adrenoceptor-mediated (EC50 = 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate alpha(2)-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [S-35]GTP gamma S binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain. British Journal of Pharmacology (2010) 159, 129-141; doi:10.1111/j.1476-5381.2009.00515.x; published online 4 December 2009
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页码:129 / 141
页数:13
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