ASTROCYTE HETEROGENEITY - ENDOGENOUS AMINO-ACID LEVELS AND RELEASE EVOKED BY NON-N-METHYL-D-ASPARTATE RECEPTOR AGONISTS AND BY POTASSIUM-INDUCED SWELLING IN TYPE-1 AND TYPE-2 ASTROCYTES
ASTROCYTE HETEROGENEITY - ENDOGENOUS AMINO-ACID LEVELS AND RELEASE EVOKED BY NON-N-METHYL-D-ASPARTATE RECEPTOR AGONISTS AND BY POTASSIUM-INDUCED SWELLING IN TYPE-1 AND TYPE-2 ASTROCYTES
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DOI：
10.1111/j.1471-4159.1992.tb10073.x
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发表时间：
1992-05-01
影响因子：
4.7
通讯作者：
PATRIZIO, M
中科院分区：
文献类型：
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作者：
LEVI, G;PATRIZIO, M
本研究的目的是确定内源性氨基酸是否在非n-甲基- d -天冬氨酸（NMDA）受体激活后从1型和2型星形胶质细胞中释放，以及这种释放是否与细胞肿胀有关。用高效液相色谱法测定了1型或2型星形胶质细胞高度富集的新生大鼠皮层二次培养物的氨基酸水平和释放。提出了以下意见。(a)几种氨基酸（谷氨酸、丙氨酸、谷氨酰胺、天冬酰胺、牛磺酸、丝氨酸和苏氨酸）的内源性水平在1型星形胶质细胞中明显高于2型星形胶质细胞。(b) 1型星形胶质细胞谷氨酰胺和牛磺酸的自发释放量高于2型星形胶质细胞；其他氨基酸的情况也类似。(c)将2型星形胶质细胞培养物暴露于50 μ m的海因酸盐或准质酸中，谷氨酸的释放增加了一倍，并导致天冬氨酸、甘氨酸、牛磺酸、丙氨酸、丝氨酸（仅在海因酸盐中）和谷氨酰胺（仅在准质酸中）的释放减少但显著增加。这些作用被拮抗剂CNQX逆转。(d)将1型星形胶质细胞培养物暴露于50-200 μ m的海因酸盐或50 μ m的半质量酸盐中，即使在用二丁基环AMP处理培养物后，也不影响内源氨基酸的释放。(e)将1型或2型星形胶质细胞培养物暴露于50 mM KCl（代替等摩尔浓度的NaCl）中，可增强牛磺酸>谷氨酸>天冬氨酸的释放。这种效果在2型星形胶质细胞中比在1型星形胶质细胞中更为明显。Veratridine （50 mu- m）未引起氨基酸释放增加。(f)在1型和2型星形胶质细胞中，高[K+]诱导的氨基酸释放似乎与细胞肿胀有关。2型星形胶质细胞的肿胀和K+诱导释放略高于1型星形胶质细胞。相比之下，盐酸盐和准盐酸盐都没有引起细胞体积的明显增加。由此得出结论，非nmda受体激动剂刺激2型星形胶质细胞释放几种内源性氨基酸（其中一些具有神经活性），而不是1型星形胶质细胞。这种效果似乎与细胞肿胀无关，细胞肿胀在1型和2型星形胶质细胞中引起不同的释放谱。1型星形胶质细胞中没有盐酸盐和准盐酸盐引起的释放，这表明这种细胞类型中非nmda受体的密度非常低。
The aim of the present study was to determine whether endogenous amino acids are released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate (NMDA) receptor activation and whether such release is related to cell swelling. Amino acid levels and release were measured by HPLC in secondary cultures from neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The following observations were made. (a) The endogenous level of several amino acids (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous release of glutamine and taurine was higher in type-1 than in type-2 astrocytes; that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures to 50-mu-M kainate or quisqualate doubled the release of glutamate and caused a lower, but significant increase in that of aspartate, glycine, taurine, alanine, serine (only in the case of kainate), and glutamine (only in the case of quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of type-1 astrocyte cultures to 50-200-mu-M kainate or 50-mu-M quisqualate did not affect endogenous amino acid release, even after treating the cultures with dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50 mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of taurine > glutamate > aspartate. The effect was somewhat more pronounced in type-2 than in type-1 astrocytes. Veratridine (50-mu-M) did not cause any increase in amino acid release. (f) The release of amino acids induced by high [K+] appeared to be related to cell swelling, in both type-1 and type-2 astrocytes. Swelling and K+-induced release were somewhat higher in type-2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused any appreciable increase in cell volume. It is concluded that non-NMDA receptor agonists stimulate the release of several endogenous amino acids (some of which are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not seem to be related to cell swelling, which causes a different release profile in both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked release in type-1 astrocytes suggests that the density of non-NMDA receptors in this cell type is very low.