Nakamura Y, Kataoka K, Ishida M, Shinozaki H
Department of Physiology, Ehime University, School of Medicine, Japan.
Neuropharmacology. 1993 Sep;32(9):833-7. doi: 10.1016/0028-3908(93)90137-r.
The effects of several diastereoisomers of L-2-(carboxycyclopropyl)glycine (CCG) on L-glutamate uptake were compared among three different preparations, glial plasmalemmal vesicles (GPV), synaptosomes and cultured astrocytes from rat hippocampus. The (2S,3S,4R)-isomer (L-CCG-III) inhibited a Na(+)-dependent high-affinity L-glutamate uptake in GPV and synaptosomes in a dose dependent manner at a micromolar range. The potency was quite similar to that of L-threo-beta-hydroxyaspartate in both subcellular fractions and much higher than L-aspartate-beta-hydroxamate, which were known as potent inhibitors of glutamate uptake. The (2S,3R,4S)-isomer (L-CCG-IV) also inhibited the glutamate uptake in GPV and synaptosomes, but it was about 100 times less active than L-CCG-III. The (2S,3S,4S)- and (2S,3R,4R)-isomers (L-CCG-I and L-CCG-II, respectively) hardly showed any inhibitory action on the glutamate uptake. Dixon plot analysis of the initial uptake rate revealed that the inhibition was in a competitive manner and the value of the inhibition constant (Ki) was about 1 microM in both GPV and synaptosomes. L-CCG-III effectively inhibited the glutamate uptake by cultured hippocampal astrocytes as well. These results suggested that L-CCG-III inhibited the glutamate uptake in both neurones and glial cells of the mammalian central nervous system in a similar manner.
比较了L-2-(羧基环丙基)甘氨酸(CCG)的几种非对映异构体对三种不同制剂中L-谷氨酸摄取的影响，这三种制剂分别是大鼠海马体的胶质细胞质膜囊泡(GPV)、突触体和培养的星形胶质细胞。(2S,3S,4R)-异构体(L-CCG-III)在微摩尔范围内以剂量依赖性方式抑制GPV和突触体中Na(+)依赖性高亲和力L-谷氨酸摄取。在两个亚细胞组分中，其效力与L-苏式-β-羟基天冬氨酸相当，远高于L-天冬氨酸-β-羟基肟酸，而后两者是已知的谷氨酸摄取有效抑制剂。(2S,3R,4S)-异构体(L-CCG-IV)也抑制GPV和突触体中的谷氨酸摄取，但其活性比L-CCG-III低约100倍。(2S,3S,4S)-和(2S,3R,4R)-异构体(分别为L-CCG-I和L-CCG-II)对谷氨酸摄取几乎没有任何抑制作用。对初始摄取速率的Dixon图分析表明，抑制作用呈竞争性，在GPV和突触体中抑制常数(Ki)值约为1 microM。L-CCG-III也有效抑制培养的海马星形胶质细胞对谷氨酸的摄取。这些结果表明，L-CCG-III以类似方式抑制哺乳动物中枢神经系统神经元和胶质细胞中的谷氨酸摄取。
