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首页> 外文期刊>The European Journal of Neuroscience >Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue.
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Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue.

机译：大麻二酚与海马组织中内源性大麻素信号传导的相互作用。

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摘要

The phytocannabinoid cannabidiol (CBD) possesses no psychotropic activity amid potentially beneficial therapeutic applications. We here characterized interactions between CBD (1 microm) and the endocannabinoid system in cultured rat hippocampal cells. The CBD-induced Ca(2+) rise observed in neurons and glia was markedly reduced in the presence of the endogenous cannabinoid anandamide in neurons, with no alteration seen in glia. Neuronal CBD responses were even more reduced in the presence of the more abundant endocannabinoid 2-arachidonyl glycerol, this action was maintained in the presence of the CB(1) receptor antagonist AM281 (100 nm). Neuronal CBD responses were also reduced by pre-exposure to glutamate, expected to increase endocannabinoid levels by increasing in [Ca(2+)](i). Application of AM281 at 1 microm elevated CBD-induced Ca(2+) responses in both cell types, further confirming our finding that endocannabinoid-mediated signalling is negatively coupled to the action of CBD. However, upregulation of endogenous levels of endocannabinoids via inhibition of endocannabinoid hydrolysis (with URB597 and MAFP) could not be achieved under resting conditions. Because Delta(9)-tetrahydrocannabinol did not mimic the endocannabinoid actions, and pertussis toxin treatment had no effect on CBD responses, we propose that the effects of AM281 were mediated via a constitutively active signalling pathway independent of CB(1) signalling. Instead, signalling via G(q/11) and phospholipase C appears to be negatively coupled to CBD-induced Ca(2+) responses, as the inhibitor U73122 enhanced CBD responses. Our data highlight the interaction between exogenous and endogenous cannabinoid signalling, and provide evidence for the presence of an additional pharmacological target, sensitive to endocannabinoids and to AM281.
机译：在潜在有益的治疗应用中，植物大麻素大麻二酚（CBD）不具有精神活性。我们在这里表征了在培养的大鼠海马细胞中CBD（1微米）和内源性大麻素系统之间的相互作用。在神经元中观察到CBD诱导的Ca（2+）升高，神经元中存在内源性大麻素南and酰胺，神经胶质中未见变化，而神经胶质中的Ca（2+）升高明显降低。在存在更丰富的内源性大麻素2-花生四烯酸甘油的情况下，神经元CBD的反应甚至进一步降低，在存在CB（1）受体拮抗剂AM281（100 nm）的情况下，这种作用得以维持。神经元的CBD反应也通过预先暴露于谷氨酸盐而降低，预计通过增加[Ca（2 +）]（i）来增加内源性大麻素水平。 AM281在1微米的应用提高了两种细胞类型中CBD诱导的Ca（2+）响应，进一步证实了我们的发现，内源性大麻素介导的信号与CBD的作用负相关。但是，在静息条件下无法通过抑制内源性大麻素水解（使用URB597和MAFP）来上调内源性内源性大麻素水平。因为Delta（9）-四氢大麻酚没有模仿内源性大麻素的作用，并且百日咳毒素治疗对CBD的反应没有影响，所以我们建议AM281的作用是通过独立于CB（1）信号传导的组成性主动信号传导途径介导的。相反，通过G（q / 11）和磷脂酶C的信号似乎与CBD诱导的Ca（2+）反应负相关，因为抑制剂U73122增强了CBD反应。我们的数据突出了外源性和内源性大麻素信号传导之间的相互作用，并提供了对内源性大麻素和AM281敏感的其他药理学目标的证据。

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