Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
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DOI：
10.1111/j.1476-5381.2010.01166.x
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发表时间：
2011-08-01
影响因子：
7.3
通讯作者：
Di Marzo, Vincenzo
中科院分区：
文献类型：
--
作者：
De Petrocellis, Luciano;Ligresti, Alessia;Di Marzo, Vincenzo
背景和目的大麻二酚 (CBD) 和 Delta(9)-四氢大麻酚 (THC) 与内源性大麻素系统的瞬时受体电位 (TRP) 通道和酶相互作用。实验方法选择含有更丰富大麻素的大麻品种的 11 种纯大麻素和植物提取物 [植物药物物质 (BDS)] 对 TRPV1、TRPV2、TRPM8、TRPA1、人重组二酰基甘油脂肪酶 a (DAGL α)、大鼠脑脂肪酸酰胺水解酶 (FAAH)、COS 细胞单酰基甘油脂肪酶 (MAGL)、人重组 N-酰基乙醇胺酰胺水解酶 (NAAA) 和 anandamide 细胞摄取 (ACU) 使用转染细胞中基于荧光的钙测定和基于放射性标记底物的酶测定对 RBL-2H3 细胞进行研究。还测试了大麻酚 (CBN)、大麻色烯 (CBC)、CBD 的酸 (CBDA、CBGA、THCA) 和丙基同系物 (CBDV、CBGV、THCV)、大麻醇 (CBG) 和 THC，以及四氢大麻二酚酸 (THCVA)。 主要结果 CBD、CBG、CBGV 和 THCV 刺激人类 TRPV1 并使之脱敏。 CBC、CBD 和 CBN 是有效的大鼠 TRPA1 激动剂和脱敏剂，但 THCV-BDS 是针对该靶点最有效的化合物。 CBG-BDS 和 THCV-BDS 是最有效的大鼠 TRPM8 拮抗剂。除 CBC 和 CBN 外，所有非酸性大麻素均能有效激活大鼠 TRPV2 并使其脱敏。 CBDV 和所有酸都会抑制 DAGL α。一些 BDS（但不是纯化合物）抑制 MAGL。 CBD是唯一抑制FAAH的化合物，而CBC>CBG>CBGV的BDS抑制NAAA。 CBC = CBG > CBD 抑制 ACU，THCVA、CBGV、CBDA 和 THCA 的 BDS 也有抑制作用，但后者提取物是更有效的抑制剂。 结论和意义这些结果与大麻素和大麻提取物的镇痛、抗炎和抗癌作用相关。
BACKGROUND AND PURPOSECannabidiol (CBD) and Delta(9)-tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels and enzymes of the endocannabinoid system.EXPERIMENTAL APPROACHThe effects of 11 pure cannabinoids and botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase a (DAGL alpha), rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol lipase (MAGL), human recombinant N-acylethanolamine acid amide hydrolase (NAAA) and anandamide cellular uptake (ACU) by RBL-2H3 cells, were studied using fluorescence-based calcium assays in transfected cells and radiolabelled substrate-based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), the acids (CBDA, CBGA, THCA) and propyl homologues (CBDV, CBGV, THCV) of CBD, cannabigerol (CBG) and THC, and tetrahydrocannabivarin acid (THCVA) were also tested.KEY RESULTSCBD, CBG, CBGV and THCV stimulated and desensitized human TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers, but THCV-BDS was the most potent compound at this target. CBG-BDS and THCV-BDS were the most potent rat TRPM8 antagonists. All non-acid cannabinoids, except CBC and CBN, potently activated and desensitized rat TRPV2. CBDV and all the acids inhibited DAGL alpha. Some BDS, but not the pure compounds, inhibited MAGL. CBD was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV, CBDA and THCA, but the latter extracts were more potent inhibitors.CONCLUSIONS AND IMPLICATIONSThese results are relevant to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts.