Department of Pharmacology and Toxicology, University of Kansas, 1251 Wescoe Hall Drive, 3048B Malott Hall, Lawrence, KS 66045, United States.
Eur Neuropsychopharmacol. 2013 Jul;23(7):760-7. doi: 10.1016/j.euroneuro.2012.06.012. Epub 2012 Jul 28.
Recent evidence suggests that cannabinoid receptor agonists may regulate serotonin 2A (5-HT(2A)) receptor neurotransmission in the brain, although no molecular mechanism has been identified. Here, we present experimental evidence that sustained treatment with a non-selective cannabinoid agonist (CP55,940) or selective CB2 receptor agonists (JWH133 or GP1a) upregulate 5-HT(2A) receptors in a neuronal cell line. Furthermore, this cannabinoid receptor agonist-induced upregulation of 5-HT(2A) receptors was prevented in cells stably transfected with either CB2 or β-Arrestin 2 shRNA lentiviral particles. Additionally, inhibition of clathrin-mediated endocytosis also prevented the cannabinoid receptor-induced upregulation of 5-HT(2A) receptors. Our results indicate that cannabinoid agonists might upregulate 5-HT(2A) receptors by a mechanism that requires CB2 receptors and β-Arrestin 2 in cells that express both CB2 and 5-HT(2A) receptors. 5-HT(2A) receptors have been associated with several physiological functions and neuropsychiatric disorders such as stress response, anxiety and depression, and schizophrenia. Therefore, these results might provide a molecular mechanism by which activation of cannabinoid receptors might be relevant to some cognitive and mood disorders in humans.
最近的证据表明，大麻素受体激动剂可能调节大脑中的血清素 2A（5-HT(2A)）受体神经传递，尽管尚未确定任何分子机制。在这里，我们提供了实验证据表明，非选择性大麻素激动剂（CP55,940）或选择性 CB2 受体激动剂（JWH133 或 GP1a）的持续治疗可上调神经元细胞系中的 5-HT(2A)受体。此外，在稳定转染 CB2 或β-Arrestin 2 shRNA 慢病毒颗粒的细胞中，这种大麻素受体激动剂诱导的 5-HT(2A)受体上调被阻止。此外，网格蛋白介导的内吞作用的抑制也阻止了大麻素受体诱导的 5-HT(2A)受体上调。我们的结果表明，大麻素激动剂可能通过一种需要 CB2 受体和β-Arrestin 2 的机制上调 5-HT(2A)受体，该机制在表达 CB2 和 5-HT(2A)受体的细胞中起作用。5-HT(2A)受体与几种生理功能和神经精神疾病有关，如应激反应、焦虑和抑郁以及精神分裂症。因此，这些结果可能为大麻素受体的激活与人类某些认知和情绪障碍相关提供了一种分子机制。
