Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia
Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia
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DOI：
10.1046/j.1471-4159.1999.721671.x
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发表时间：
1999-04-01
影响因子：
4.7
通讯作者：
Boddeke, HWGM
中科院分区：
文献类型：
--
作者：
Biber, K;Laurie, DJ;Boddeke, HWGM
用兴奋性神经递质谷氨酸刺激星形胶质细胞导致肌醇1，4，5-三磷酸的形成和随后的细胞内钙含量的增加。星形胶质细胞表达亲离子型受体和亲代谢型谷氨酸（mGlu）受体，其中mGlu（5）受体可能参与谷氨酸诱导的钙信号传导。mGlu（5）受体以两种剪接变体mGlu和mGlu（5 α）的形式存在，但迄今为止还不知道哪种剪接变体负责星形胶质细胞中谷氨酸诱导的效应。我们在此报告编码mGlu（5）受体剪接变体的两种mRNA均由培养的星形胶质细胞表达。mGlu（5a）受体mRNA的表达明显强于mGlu（5 b）受体mRNA的表达。原位杂交结果显示，成年大鼠前脑有mGlu（5a）受体mRNA的表达，而嗅球有较强的mGlu（5a）mRNA表达。大脑其余部分中mGlu（5a）受体mRNA的信号弥漫且微弱，但始终高于背景。星形胶质细胞中mGlu（5）受体的激活导致磷酸肌醇产生和瞬时钙反应增加。令人惊讶的是，激动剂效力的等级顺序[使君子酸]（2S，1'S，2'S）-2-（羧基环丙基）甘氨酸=反式-（1 S，3R）-1-氨基-1，3-环戊烷二羧酸（1 S，3R-ACPD）>谷氨酸]与重组表达mGlu（5 a）受体的报道不同。在培养的小胶质细胞中也发现了3R-ACPD诱导的钙信号，这首次表明mGlu（5a）受体在这些巨噬细胞样细胞中表达。
Stimulation of astrocytes with the excitatory neurotransmitter glutamate leads to the formation of inositol 1,4,5-trisphosphate and the subsequent increase of intracellular calcium content. Astrocytes express both ionotropic receptors and metabotropic glutamate (mGlu) receptors, of which mGlu(5) receptors are probably involved in glutamate-induced calcium signaling. The mGlu(5) receptor occurs as two splice variants, mGlu,, and mGlu(5a), but it was hitherto unknown which splice Variant is responsible for the glutamate-induced effects in astrocytes, We report here that both mRNAs encoding mGlu(5) receptor splice variants are expressed by cultured astrocytes. The expression of mGlu(5a) receptor mRNA is much stronger than that of mGlu(5b) receptor mRNA in these cells. In situ hybridization experiments reveal neuronal expression of mGlu(5a) receptor mRNA in adult rat forebrain but a strong neuronal expression of mGlu(5a) mRNA only in olfactory bulb. Signals for mGlu(5a) receptor mRNA in the rest of the brain were diffuse and weak but consistently above background. Activation of mGlu(5) receptors in astrocytes yields increases in inositol phosphate production and transient calcium responses. It is surprising that the rank order of agonist potency [quisqualate > (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine = trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R-ACPD) > glutamate] differs from that reported for recombinantly expressed mGlu(5a) receptors, The expression of mGlu(5a) receptor mRNA and the occurrence of 1S,3R-ACPD-induced calcium signaling were found also in cultured microglia, indicating for the first time expression of mGlu(5a) receptors in these macrophage-like cells.