Ethanol alters glutamate but not adenosine uptake in rat astrocytes: Evidence for protein kinase C involvement
Ethanol alters glutamate but not adenosine uptake in rat astrocytes: Evidence for protein kinase C involvement
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DOI：
10.1023/a:1014955111742
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Parkinson, FE
中科院分区：
文献类型：
--
作者：
Othman, T;Sinclair, CJD;Parkinson, FE
谷氨酸是大脑中主要的兴奋性神经递质。通过刺激神经元活动，谷氨酸增加细胞能量利用，增强ATP水解，促进腺苷的形成。腺苷具有受体介导的作用，可减少或对抗谷氨酸的兴奋作用。作为乙醇抑制谷氨酸兴奋作用和增强腺苷抑制作用的可能机制，我们验证了乙醇促进[H-3]谷氨酸摄取和抑制[H-3]腺苷摄取的假设。通过对大鼠星形胶质细胞的原代培养，我们发现乙醇急性处理（50 ram, 30 min）抑制[H-3]谷氨酸摄取，并减少蛋白激酶C （PKC）诱导的[H-3]谷氨酸摄取的刺激。然而，长时间乙醇处理（50 mM， 3天）增加了[H-3]谷氨酸摄取和PKC活性。与其他细胞类型相反，急性或慢性乙醇暴露均不影响星形胶质细胞的[H-3]腺苷摄取。这些数据表明，在大鼠皮质星形胶质细胞中，乙醇通过影响PKC对转运蛋白活性的调节影响[H-3]谷氨酸的摄取，而不是[H-3]腺苷的摄取。
Glutamate is the primary excitatory neurotransmitter in brain. By stimulating neuronal activity, glutamate increases cellular energy utilization, enhances ATP hydrolysis and promotes the formation of adenosine. Adenosine has receptor-mediated effects that reduce or oppose the excitatory effects of glutamate. As a possible mechanism for ethanol's ability to inhibit excitatory effects of glutamate and enhance inhibitory effects of adenosine, we tested the hypothesis that ethanol promotes [H-3]glutamate uptake and inhibits [H-3]adenosine uptake. Using primary cultures of rat astrocytes, we found that acute treatment with ethanol (50 ram, 30 min) inhibited [H-3]glutamate uptake and reduced protein kinase C (PKC)-induced stimulation of [H-3]glutamate uptake. Prolonged treatment (50 mM, 3 day) with ethanol, however, increased both [H-3]glutamate uptake and PKC activity. Contrary to other cell types, neither acute or chronic ethanol exposure affected [H-3]adenosine uptake in astrocytes. These data indicate that in rat cortical astrocytes ethanol affects [H-3]glutamate uptake but not [H-3]adenosine uptake by affecting PKC modulation of transporter activity.