Pharmacology, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Ibaraki, Japan.
J Neurosci Res. 2010 Aug 1;88(10):2252-62. doi: 10.1002/jnr.22382.
Periodic and spontaneous Ca(2+) spikes are observed in neurons during development of the central nervous system, and spontaneous changes in intracellular Ca(2+) concentration in neurons play important roles in the development of neural circuits. To clarify the roles of metabotropic glutamate receptors (mGluRs) in the regulation of spontaneous Ca(2+) spikes, we investigated the effects of selective and nonselective mGluRs ligands on primary cultures of rat cortical neurons. Cultured cortical neurons expressed all eight mGluR subtypes on reverse transcription-PCR. The mGluR2 and mGluR3 agonists LY379268, LY354740, and (2R,4R)-APDC increased the amplitude but decreased the frequency of spontaneous Ca(2+) spikes in cultured cortical neurons. The effects of these mGluR2 and mGluR3 agonists were completely inhibited by the presence of a potent mGluR2 and mGluR3 antagonist, LY341495, and by pretreatment with pertussis toxin. No significant effect was observed with either activation or inhibition of mGluR1, mGluR4, mGluR5, mGluR6, mGluR7, and mGluR8 on the spontaneous Ca(2+) spikes in cultured cortical neurons. These findings indicate that, among mGluRs, the group II mGluR subtypes mGluR2 and mGluR3 play principal roles in modulation of spontaneous Ca(2+) spikes.
在中枢神经系统发育过程中，神经元中会观察到周期性和自发性 Ca(2+) spikes，神经元中细胞内 Ca(2+) 浓度的自发性变化在神经回路的发育中发挥重要作用。为了阐明代谢型谷氨酸受体 (mGluRs) 在调节自发性 Ca(2+) spikes 中的作用，我们研究了选择性和非选择性 mGluRs 配体对原代培养的大鼠皮质神经元的影响。培养的皮质神经元在反转录-PCR 上表达所有 8 种 mGluR 亚型。mGluR2 和 mGluR3 激动剂 LY379268、LY354740 和 (2R,4R)-APDC 增加了培养的皮质神经元中自发性 Ca(2+) spikes 的幅度，但降低了其频率。这些 mGluR2 和 mGluR3 激动剂的作用可被强效 mGluR2 和 mGluR3 拮抗剂 LY341495 的存在以及预先用百日咳毒素处理完全抑制。在培养的皮质神经元中，mGluR1、mGluR4、mGluR5、mGluR6、mGluR7 和 mGluR8 的激活或抑制对自发性 Ca(2+) spikes 均无明显影响。这些发现表明，在 mGluRs 中，II 组 mGluR 亚型 mGluR2 和 mGluR3 在调节自发性 Ca(2+) spikes 方面发挥主要作用。
