Agonistic properties of cannabidiol at 5-HT1a receptors
Agonistic properties of cannabidiol at 5-HT1a receptors
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DOI：
10.1007/s11064-005-6978-1
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发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Parker, KK
中科院分区：
文献类型：
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作者：
Russo, EB;Burnett, A;Parker, KK
大麻二酚 (CBD) 是大麻的一种主要的、具有生物活性但不具有精神活性的成分。在这份基于细胞培养的报告中，CBD 以浓度依赖性方式从克隆的人 5-HT1a 受体中取代激动剂 [3H]8-OH-DPAT。相比之下，大麻的主要精神活性成分四氢大麻酚 (THC) 在相同的微摩尔浓度范围内不会取代受体的激动剂。在信号转导研究中，CBD 作为人类 5-HT1a 受体的激动剂，如两种相关方法所示。首先，CBD 增加了 G 蛋白偶联受体系统中的 [35S]GTP gamma S 结合，就像已知的激动剂血清素一样。其次，在这个与 cAMP 产生负耦合的 GPCR 系统中，根据位移数据，CBD 和 5-HT 都会以相似的受体占据表观水平降低 cAMP 浓度。克隆大鼠 5-HT2a 受体的初步比较数据表明，在结合分析中，CBD 具有活性，但相对于人类 5-HT1a 受体活性较低。总体而言，这些研究表明 CBD 是人类 5-HT1a 受体的适度亲和力激动剂。需要开展更多工作来比较 CBD 对其他血清素受体和其他物种的潜力。最后，结果表明大麻二酚可能具有超越大麻素受体领域的有趣且有用的潜力。
Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTP gamma S binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively coupled to cAMP production, both CBD and 5-HT decrease cAMP concentration at similar apparent levels of receptor occupancy, based upon displacement data. Preliminary comparative data is also presented from the cloned rat 5-HT2a receptor suggesting that CBD is active, but less so, relative to the human 5-HT1a receptor, in binding analyses. Overall, these studies demonstrate that CBD is a modest affinity agonist at the human 5-HT1a receptor. Additional work is required to compare CBD's potential at other serotonin receptors and in other species. Finally, the results indicate that cannabidiol may have interesting and useful potential beyond the realm of cannabinoid receptors.