METHYLMERCURY-INDUCED ALTERATIONS IN EXCITATORY AMINO-ACID-TRANSPORT IN RAT PRIMARY ASTROCYTE CULTURES
METHYLMERCURY-INDUCED ALTERATIONS IN EXCITATORY AMINO-ACID-TRANSPORT IN RAT PRIMARY ASTROCYTE CULTURES
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DOI：
10.1016/0006-8993(93)90680-l
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发表时间：
1993-02-05
期刊：
影响因子：
2.9
通讯作者：
KIMELBERG, HK
中科院分区：
文献类型：
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作者：
ASCHNER, M;DU, YL;KIMELBERG, HK
为了确定甲基汞（MeHg）是否有可能干扰新生大鼠皮质原代星形胶质细胞培养物的稳态功能，甲基汞对L-谷氨酸和D-天冬氨酸的摄取和流出的影响进行了研究。当甲基汞浓度低至10（-5）M时，这两种兴奋性氨基酸（EAA）的摄取均显著降低（P < 0.05）。从预装星形胶质细胞的谷氨酸和天冬氨酸流出也增加了甲基汞的剂量和时间依赖性的方式。由于在我们早期的研究中，我们已经发现，甲基汞导致剂量依赖性的星形胶质细胞肿胀，这可能是增加外排的机制，我们研究了是否有牵连的星形胶质细胞肿胀的导电离子通量的阻塞，可以扭转甲基汞诱导的L-谷氨酸和D-天冬氨酸外排的增加。在最大浓度下测试了抑制低渗介质诱导的EAA外排的三种化合物，4-乙酰氨基-4 '-异硫氰酸基芪-2，2'-二磺酸（SITS）、L-644，711（依他尼酸的衍生物）和呋塞米逆转甲基汞诱导的EAA外排的能力。只有呋塞米（5 mM）可以维持逆转的整个120分钟的持续时间的外排测量。由于低渗介质肿胀诱导的EAA释放被这些阴离子抑制剂抑制（按以下顺序：L-644，711> SITS >呋塞米），我们得出结论，不同的机制占EAA释放从原代星形胶质细胞培养在甲基汞暴露相比，低渗介质诱导的流出。
To determine whether methylmercury (MeHg) has the potential to interfere with homeostatic functions in neonatal rat cortical primary astrocyte cultures, the effects of MeHg on the uptake and efflux of both L-glutamate and D-aspartate were examined. Uptake of both of these excitatory amino acids (EAAs) was significantly (P < 0.05) reduced in the presence of MeHg concentrations as low as 10(-5) M. Efflux of both glutamate and aspartate from preloaded astrocytes was also increased by MeHg in a dose- and time-dependent fashion. Since in our earlier studies we had found that MeHg causes dose-dependent astrocytic swelling, which could have been the mechanism of the increased efflux, we examined whether blockage of conductive ion fluxes, which have been implicated in astrocytic swelling, could reverse the MeHg-induced increase in L-glutamate and D-aspartate efflux. Three compounds which inhibit the hypotonic-media-induced efflux of EAA, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), L-644,711 (a derivative of ethacrynic acid) and furosemide were tested al their maximal concentrations for their ability to reverse MeHg-induced EAA efflux. Only furosemide (5 mM) could sustain the reversal for the entire 120 min duration of the efflux measurement. Since hypotonic-media swelling-induced release of EAAs is inhibited by these anion inhibitors (in the following rank order: L-644,711 > SITS > furosemide), we conclude that different mechanisms account for EAA release from primary astrocyte cultures during MeHg exposure as compared to hypotonic media-induced efflux.