Gallo V, Suergiu R, Giovannini C, Levi G
Department of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
J Neurochem. 1987 Dec;49(6):1801-9. doi: 10.1111/j.1471-4159.1987.tb02439.x.
Using cerebellar, neuron-enriched primary cultures, we have studied the glutamate receptor subtypes coupled to neurotransmitter amino acid release. Acute exposure of the cultures to micromolar concentrations of kainate and quisqualate stimulated D-[3H]aspartate release, whereas N-methyl-D-aspartate, as well as dihydrokainic acid, were ineffective. The effect of kainic acid was concentration dependent in the concentration range of 20-100 microM. Quisqualic acid was effective at lower concentrations, with maximal releasing activity at about 50 microM. Kainate and dihydrokainate (20-100 microM) inhibited the initial rate of D-[3H]aspartate uptake into cultured granule cells, whereas quisqualate and N-methyl-DL-aspartate were ineffective. D-[3H]Aspartate uptake into confluent cerebellar astrocyte cultures was not affected by kainic acid. The stimulatory effect of kainic acid on D-[3H]aspartate release was Na+ independent, and partly Ca2+ dependent; the effect of quisqualate was Na+ and Ca2+ independent. Kynurenic acid (50-200 microM) and, to a lesser extent, 2,3-cis-piperidine dicarboxylic acid (100-200 microM) antagonized the stimulatory effect of kainate but not that of quisqualate. Kainic and quisqualic acid (20-100 microM) also stimulated gamma-[3H]-aminobutyric acid release from cerebellar cultures, and kynurenic acid antagonized the effect of kainate but not that of quisqualate. In conclusion, kainic acid and quisqualic acid appear to activate two different excitatory amino acid receptor subtypes, both coupled to neurotransmitter amino acid release. Moreover, kainate inhibits D-[3H]aspartate neuronal uptake by interfering with the acidic amino acid high-affinity transport system.
利用富含神经元的小脑原代培养物，我们研究了与神经递质氨基酸释放相关的谷氨酸受体亚型。将培养物急性暴露于微摩尔浓度的海人酸和quisqualate可刺激D-[3H]天冬氨酸释放，而N-甲基-D-天冬氨酸以及二氢海人酸则无效。在20-100 microM的浓度范围内，海人酸的作用呈浓度依赖性。quisqualic酸在较低浓度下有效，最大释放活性约为50 microM。海人酸和二氢海人酸（20-100 microM）抑制培养的颗粒细胞中D-[3H]天冬氨酸的初始摄取速率，而quisqualate和N-甲基-DL-天冬氨酸则无效。D-[3H]天冬氨酸摄取到汇合的小脑星形胶质细胞培养物中不受海人酸的影响。海人酸对D-[3H]天冬氨酸释放的刺激作用不依赖于Na+，部分依赖于Ca2+；quisqualate的作用不依赖于Na+和Ca2+。犬尿喹啉酸（50-200 microM）以及在较小程度上的2,3-顺式哌啶二羧酸（100-200 microM）拮抗海人酸的刺激作用，但不拮抗quisqualate的刺激作用。海人酸和quisqualic酸（20-100 microM）也刺激小脑培养物中γ-[3H]-氨基丁酸的释放，犬尿喹啉酸拮抗海人酸的作用，但不拮抗quisqualate的作用。总之，海人酸和quisqualic酸似乎激活了两种不同的兴奋性氨基酸受体亚型，两者均与神经递质氨基酸释放相关。此外，海人酸通过干扰酸性氨基酸高亲和力转运系统抑制D-[3H]天冬氨酸的神经元摄取。
