To date, several studies have demonstrated that phospholipase C-coupled receptors stimulate the production of endocannabinoids, particularly 2-arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation of the 5-HT(2A) receptor leads to the production and release of the endocannabinoid 2-arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5-HT(2A) receptor were first incubated with [(3)H]-arachidonic acid for 24 h. Following stimulation with 10 mum serotonin, lipids were extracted from the assay medium, separated by thin layer chromatography, and analyzed by liquid scintillation counting. Our results indicate that 5-HT(2A) receptor activation stimulates the formation and release of 2-arachidonoylglycerol. The 5-HT(2A) receptor-dependent release of 2-arachidonoylglycerol was partially dependent on phosphatidylinositol-specific phospholipase C activation. Diacylglycerol produced downstream of 5-HT(2A) receptor-mediated phospholipase D or phosphatidylcholine-specific phospholipase C activation did not appear to contribute to 2-arachidonoylglycerol formation in NIH3T3-5HT(2A) cells. In conclusion, our results support a functional model where neuromodulatory neurotransmitters such as serotonin may act as regulators of endocannabinoid tone at excitatory synapses through the activation of phospholipase C-coupled G-protein coupled receptors.

译文

迄今为止,一些研究表明磷脂酶C偶联受体刺激内源性大麻素的产生,特别是2-花生四烯基甘油。现在有证据表明,内源性大麻素在大鼠和小鼠中均参与磷脂酶C偶联5-羟色胺 (2A) 受体介导的行为作用。这项研究的主要目的是确定5-HT(2A) 受体的激活是否导致内源性大麻素2-花生四烯基甘油的产生和释放。首先将稳定表达大鼠5-HT(2A) 受体的NIH3T3细胞与 [(3)H]-花生四烯酸孵育24小时。用10 mum 5-羟色胺刺激后,从测定培养基中提取脂质,通过薄层色谱分离,并通过液体闪烁计数进行分析。我们的结果表明,5-HT(2A) 受体激活刺激2-花生四烯基甘油的形成和释放。2-花生四烯基甘油的5-HT(2A) 受体依赖性释放部分依赖于磷脂酰肌醇特异性磷脂酶C活化。在5-HT(2A) 受体介导的磷脂酶D或磷脂酰胆碱特异性磷脂酶C激活下游产生的二酰基甘油似乎没有促进NIH3T3-5HT(2A) 细胞中2-花生四烯基甘油的形成。总之,我们的结果支持了一种功能模型,其中神经调节神经递质 (例如5-羟色胺) 可以通过激活磷脂酶C偶联g蛋白偶联受体在兴奋性突触中充当内源性大麻素调的调节剂。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录