Excitatory amino acid-induced toxicity in chick retina: amino acid release, histology, and effects of chloride channel blockers.
Excitatory amino acid-induced toxicity in chick retina: amino acid release, histology, and effects of chloride channel blockers.
复制标题
鸡视网膜兴奋性氨基酸诱导的毒性：氨基酸释放、组织学和氯离子通道阻滞剂的作用。
DOI：
10.1111/j.1471-4159.1989.tb08559.x
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发表时间：
1989
影响因子：
4.7
通讯作者：
Nicklas,WJ
中科院分区：
文献类型：
--
作者：
Zeevalk,GD;Hyndman,AG;Nicklas,WJ
通过测量内源性氨基酸释放和组织学，评价了鸡胚视网膜的急性兴奋性毒性和C1−通道阻滞剂预防毒性的能力。用红藻氨酸盐、使君子酸盐或N-甲基-D-天冬氨酸盐处理视网膜导致γ-氨基丁酸和牛磺酸的大量剂量依赖性释放，谷氨酰胺和丙氨酸的中度释放，以及谷氨酸盐或天冬氨酸盐的不可测量释放。诱导最大γ-氨基丁酸释放的浓度为50 μ M使君子酸、100 μ M红藻氨酸和100 μM N-甲基-D-天冬氨酸。用1 mM谷氨酸处理导致显著的γ-氨基丁酸释放，以及中等天冬氨酸水平升高。典型的兴奋毒性视网膜病变产生的激动剂，并在较低的浓度测试，显示了区域的敏感性。γ-氨基丁酸释放量与组织肿胀程度呈正相关，表明释放可能继发于毒性细胞事件。C1−的缺失完全阻断了红藻氨酸盐或谷氨酸盐的细胞毒性作用。同样，加入600 μ M的C1−/碳酸氢根阴离子通道阻断剂4，4 ′-二异硫氰酸芪-2，2 ′-二磺酸盐可保护视网膜免受所有兴奋性毒性类似物的细胞毒性损伤，并使氨基酸水平恢复至基线值。速尿。阻断Na+/K+/2C 1 −共转运，在减少由激动剂诱导的氨基酸释放方面效果甚微。与后者一致，组织学检查显示病变持续存在，但细胞水肿普遍减轻。这些结果表明，虽然C1−内流是急性兴奋性毒性现象的核心组成部分，但可能涉及被动Cl−通量以外的机制。
Acute excitotoxicity in embryonic chick retina and the ability of C1−channel blockers to prevent toxicity were evaluated by measurement of endogenous amino acid release and histology. Treatment of retina with kainate, quisqualate, orN‐methyl‐D‐aspartate resulted in a large dose‐dependent release of γ‐aminobutyric acid and taurine, moderate release of glutamine and alanine, and no measurable release of glu‐tamate or aspartate. Concentrations inducing maximal γ‐aminobutyric acid release were 50 μMquisqualate, 100 μMkainate, and 100 μM N‐methyl‐D‐aspartate. Treatment with 1 mMglutamate resulted in significant γ‐aminobutyric acid release, as well as an elevation in medium aspartate levels. Typical excitotoxic retinal lesions were produced by the agonists and, at the lower concentrations tested, revealed a regional sensitivity. There was a positive correlation between the amount of γ‐aminobutyric acid release and the extent of tissue swelling, suggesting that release may be secondary to toxic cellular events. Omission of C1−completely blocked cytotoxic effects due to kainate or glutamate. Likewise, addition of the C1−/bicarbonate anion channel blocker 4,4′‐di‐isothiocyanatostilbene‐2,2′‐disulfonate at 600 μMprotected retina from cytotoxic damage from all excitotoxic analogs and restored amino acid levels to baseline values. Furosemide. which blocks Na+/K+/2C1−cotransport, was only minimally effective in reducing amino acid release induced by the agonists. Consistent with the latter, histological examination showed the continued presence of the lesion but with general reduction of cellular edema. These results indicate that although influx of C1−is a central component of the acute excitotoxic phenomenon, mechanisms other than passive Cl−flux may be involved.