Characterization of ionotropic glutamate receptors in human lymphocytes
Characterization of ionotropic glutamate receptors in human lymphocytes
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DOI：
10.1038/sj.bjp.0704134
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发表时间：
2001-07-01
影响因子：
7.3
通讯作者：
Fantozzi, R
中科院分区：
文献类型：
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作者：
Lombardi, G;Dianzani, C;Fantozzi, R
1.用抗CD_3单克隆抗体（mAb）或植物血凝素（PHA）诱导的淋巴细胞内Ca ~（2+）浓度，研究了谷氨酸（GIu）对人淋巴细胞功能的影响（[Ca 2 +]（i））升高（Fura-2方法）和细胞增殖2Glu（0.001-100 μ M）不改变基础淋巴细胞[Ca ~（2+）]i，但显著增强抗CD 3 mAb或PHA的作用。相对于静息细胞的最大[Ca 2 +]（i）升高为：3.0 x 10（-2）mg/ml（-1）抗CD 3 mAb时为165 +/-8和247 +/-10 nM; 201 +/-4和266 +/-9 nM，5.0 × 10（-2）mg/ml（-1）PHA，不存在或存在1 μ M GIu，Glu效应呈钟形浓度依赖关系，最大（与Gill未处理的细胞相比，抗CD 3 mAb为+90 +/-3%，PHA为+57 +/-2%）。4非NMDA受体激动剂（1 μ M）显示出更大的功效（对于（S）-AMPA为+76 +/-2%;对于KA为+7 +/-4%），如果与NMDA（+46 +/-2%）或Glu本身相比。5离子型Glu受体拮抗剂完全抑制相应的特异性受体激动剂（1 μ M）的作用。计算的IC 50值为：D-APS为0.9 μ M;（+）-MK 801为0.6 μ M; NBQX为0.3 μ M。NBQX和KYNA都能够消除GI;效应。计算的IC（50）为：NBQX为3.4 μ M; KYNA.6 GIu为0.4 μ M（0.1-1 mM）不改变静息细胞增殖，而GIu（1 mM）显著抑制静息细胞增殖。（-27 +/-4%）PHA 72小时（1.0 x 10（-2）mg ml（-1））诱导的淋巴细胞增殖。7总之，人淋巴细胞表达离子型GIu受体，其在功能上作为细胞活化的调节剂起作用。
1. The effect of L-glutamate (GIu) on human lymphocyte function was studied by measuring anti-CD3 monoclonal antibody (mAb) or phytohaemagglutinin (PHA)-induced intracellular Ca2+ ([Ca2+](i)) rise (Fura-2 method), and cell proliferation (MTT assay).2 Glu (0.001-100 muM) did not modify basal lymphocyte [Ca2+]i, but significantly potentiated the effects of anti-CD3 mAb or PHA. Maximal [Ca2+](i) rises over resting cells were: 165 +/-8 and 247 +/- 10 nM at 3.0 x 10(-2) mg ml(-1) anti-CD3 mAb; 201 +/-4 and 266 +/-9 nM at 5.0 x 10(-2) mg ml(-1) PHA, in the absence or presence of 1 muM GIu, respectively.3 The Glu effect showed a bell-shape concentration-dependent relationship, with a maximum (+90 +/-3% for anti-CD3 mAb and +57 +/-2% for PHA over Gill-untreated cells) at 1 muM.4 Non-NMDA receptor agonists (1 muM) showed a greater efficacy (+76 +/-2% for (S)-AMPA; +7 +/-4% for KA), if compared to NMDA (+46 +/-2%), or Glu itself.5 Ionotropic Glu receptor antagonists completely inhibited the effects of the corresponding specific receptor agonists (1 muM). The IC50 values calculated were: 0.9 muM for D-APS: 0.6 muM for (+)-MK801; 0.3 muM for NBQX. Both NBQX and KYNA were able to abolish GI; effect. The IC(50)s calculated were: 3.4 muM for NBQX; 0.4 muM for KYNA.6 GIu (0.1-1 mM) did not change the resting cell proliferation, whereas GIu (I mM) significant inhibited (-27 +/-4%) PHA (1.0 x 10(-2) mg ml(-1))-induced lymphocyte proliferation at 72 h.7 In conclusion, human lymphocytes express ionotropic GIu receptors functionally operating as modulators of cell activation.