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首页> 美国卫生研究院文献>The Journal of Neuroscience >Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Augments cAMP Accumulation in Striatal Neurons: Evidence for a Gs Linkage to the CB1 Receptor
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Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Augments cAMP Accumulation in Striatal Neurons: Evidence for a Gs Linkage to the CB1 Receptor

机译：大麻素CB1和多巴胺D2受体的同时刺激增强了纹状体神经元中cAMP的积累：Gs链接到CB1受体的证据。

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Cannabinoids act at the CB1 receptor to inhibit adenylate cyclase activity via a pertussis toxin-sensitive G-protein. Within the striatum, CB1 receptors have been shown to be localized on the same neurons as Gi-coupled dopamine D2 receptors. In this study we have examined the interactions of CB1 and D2 receptors on adenylate cyclase. In striatal neurons in primary culture, both the CB1 receptor agonist [3-(1,1-dimethylheptyl)-11-hydroxy-Δ8tetrahydrocannabinol] (HU210) and the D2 receptor agonist quinpirole inhibited forskolin-stimulated cAMP accumulation when applied separately. In contrast, HU210 and quinpirole in combination augmented cAMP accumulation. This augmentation was blocked by the CB1 receptor antagonist SR141716A or the D2 antagonist sulpride. Pertussis toxin treatment of striatal neurons prevented the inhibition of cAMP accumulation by D2 receptors but unmasked a cannabinoid receptor-mediated stimulatory effect on cAMP accumulation. The cannabinoid receptor-stimulated accumulation of cAMP was blocked in a concentration-dependent manner by SR141716A, suggesting that the response was regulated through the CB1 receptor. Similar augmentation of cAMP accumulation after pertussis toxin treatment was observed in Chinese hamster ovary (CHO) cells transfected with, and stably expressing, the CB1 receptor. This stimulation of cAMP was not Ca2+-sensitive and was unaffected by a range of protein kinase inhibitors. Treatment of the pertussis toxin-treated cells with cholera toxin before CB1 receptor activation amplified the stimulatory pathway, suggesting that this response was mediated through a Gs-type G-protein. Stimulation of cAMP accumulation was not observed after pertussis toxin treatment of CHO cells expressing the human CB2 receptor, suggesting that this novel signaling pathway is unique to the cannabinoid CB1 receptor.
机译：大麻素通过百日咳毒素敏感的G蛋白作用于CB1受体，以抑制腺苷酸环化酶的活性。在纹状体内，已证明CB1受体与Gi偶联的多巴胺D2受体位于同一神经元上。在这项研究中，我们检查了腺苷酸环化酶上CB1和D2受体的相互作用。在原代培养的纹状体神经元中，CB1受体激动剂[3-（1,1-二甲基庚基）-11-羟基-Δ 8 四氢大麻酚]（HU210）和D2受体激动剂喹吡罗均抑制毛喉素-单独使用时，可刺激cAMP积累。相反，HU210和喹吡罗的组合增加了cAMP的积累。这种增加被CB1受体拮抗剂SR141716A或D2拮抗剂舒普利特阻断。百日咳毒素治疗纹状体神经元阻止了D2受体对cAMP积累的抑制，但没有显示大麻素受体介导的对cAMP积累的刺激作用。 SR141716A以浓度依赖的方式阻止了大麻素受体刺激的cAMP积累，表明该反应是通过CB1受体调节的。在转染并稳定表达CB1受体的中国仓鼠卵巢（CHO）细胞中，观察到百日咳毒素处理后cAMP积累的类似增加。 cAMP的这种刺激对Ca 2 + 不敏感，并且不受一系列蛋白激酶抑制剂的影响。在CB1受体激活之前，用霍乱毒素处理百日咳毒素处理过的细胞会放大刺激途径，这表明该反应是通过Gs型G蛋白介导的。百日咳毒素处理表达人CB2受体的CHO细胞后，未观察到cAMP积累的刺激，表明这种新的信号传导途径是大麻CB1受体所特有的。

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