Aluminum inhibits glutamate release from transverse rat hippocampal slices: role of G proteins, Ca channels and protein kinase C.
Aluminum inhibits glutamate release from transverse rat hippocampal slices: role of G proteins, Ca channels and protein kinase C.
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发表时间：
1992
期刊：
影响因子：
3.4
通讯作者：
S. D. Provan;R. Yokel
中科院分区：
文献类型：
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作者：
S. D. Provan;R. Yokel
铝（Al）已被证明会导致学习和记忆缺陷。本实验测试的假设，铝诱导的学习抑制可能是由于其对谷氨酸释放的影响继发于钙通道功能和/或细胞内事件触发谷氨酸释放的变化。铝以浓度依赖性方式（IC 50 = 40 μ M）抑制钙依赖性钾（K）诱发的大鼠海马400 μ m横切片[14 C]-谷氨酸释放。铝（30，100 μ M）非竞争性抑制Bay K 8644诱发的谷氨酸释放. 4-氨基吡啶（30，1000 μ M）非竞争性衰减铝抑制谷氨酸释放，表明铝诱导的钙通道功能的改变。由R（-）苯基异丙基腺苷（PIA; 1 μ M）激活Gi蛋白使K-诱发的谷氨酸释放减少69%，而300 μ M Al产生84%的减少。这些作用被Gi蛋白抑制剂N-乙基马来酰亚胺（NEM; 100 μ M）阻止，表明Al对Gi蛋白的作用抑制谷氨酸释放。300 μ M铝和80 μ M多粘菌素B抑制佛波醇肉豆蔻酸酯乙酸酯（0.16 μ M）诱导的谷氨酸释放，表明铝调节蛋白激酶C（PKC）诱导的谷氨酸释放。这些结果表明，Al对谷氨酸释放的抑制可能由多种但相互关联的机制（例如，通过与Ca系统的相互作用），为Al诱导的神经元功能改变提供多个靶点。
Aluminum (Al) has been shown to produce deficits in learning and memory. The present experiments tested the hypothesis that Al-induced inhibition of learning may be due to its effect on glutamate release secondary to changes in calcium channel function and/or intracellular events triggering glutamate release. Calcium-dependent potassium (K)-evoked [14C]-glutamate release from 400 microns transverse rat hippocampal slices was inhibited by Al in a concentration dependent manner (IC50 = 40 microM). Aluminum (30, 100 microM) noncompetitively inhibited Bay K 8644-evoked glutamate release. 4-Aminopyridine (30, 1000 microM) noncompetitively attenuated the Al inhibition of glutamate release, suggesting an Al-induced alteration of Ca channel function. Activation of the Gi protein by R(-)phenylisopropyladenosine (PIA; 1 microM) reduced K-evoked glutamate release 69%, whereas 300 microM Al produced an 84% reduction. These effects were prevented by the Gi protein inhibitor N-ethylmaleimide (NEM; 100 microM), suggesting an effect of Al on the Gi protein to inhibit glutamate release. Phorbol myristate acetate (0.16 microM)-induced glutamate release was inhibited by 300 microM Al and 80 microM polymyxin B, suggesting an Al modulation of protein kinase C (PKC)-evoked glutamate release. These results demonstrate an Al inhibition of glutamate release that may be mediated by multiple, but interconnected mechanisms (e.g., via interactions with Ca systems), providing multiple targets for an Al-induced alteration of neuronal function.