Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain.
Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain.
复制标题
Cyclothiazide 调节大鼠大脑培养神经元中 AMPA 受体介导的细胞内游离 Ca2 和 Mg2 的增加。
DOI：
10.1046/j.1471-4159.1995.64052049.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Reynolds,IJ
中科院分区：
文献类型：
--
作者：
Hoyt,KR;Rajdev,S;Fattman,CL;Reynolds,IJ
We investigated the modulation of (±)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐induced increases in intracellular free Ca2+([Ca2+]i) and intracellular free Mg2+([Mg2+]i) by cyclothiazide and GYKI 52466 using microspectrofluorimetry in single cultured rat brain neurons. AMPA‐induced changes in [Ca2+]iwere increased by 0.3–100 µMcyclothiazide, with an EC50value of 2.40 µMand a maximum potentiation of 428% of control values. [Ca2+]iresponses to glutamate in the presence ofN‐methyl‐d‐aspartate (NMDA) receptor antagonists were also potentiated by 10 µMcyclothiazide. The response to NMDA was not affected, demonstrating specificity of cyclothiazide for non‐NMDA receptors. Almost all neurons responded with an increase in [Ca2+]ito both kainate and AMPA in the absence of extracellular Na+, and these Na+‐free responses were also potentiated by cyclothiazide. GYKI 52466 inhibited responses to AMPA with an IC50value of 12.0 µM. Ten micromolar cyclothiazide significantly decreased the potency of GYKI 52466. However, the magnitude of this decrease in potency was not consistent with a competitive interaction between the two ligands. Cyclothiazide also potentiated AMPA‐ and glutamate‐induced increases in [Mg2+]i. These results are consistent with the ability of cyclothiazide to decrease desensitization of non‐NMDA glutamate receptors and may provide the basis for the increase in non‐NMDA receptor‐mediated excitotoxicity produced by cyclothiazide.
