Astrocyte swelling in liver failure: role of glutamine and benzodiazepines.

M D Norenberg, A S Bender
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引用次数: 136

Abstract

We examined the effect of methionine sulfoximine (MSO) and peripheral benzodiazepine (BZD) ligands on ammonia-induced swelling of primary astrocyte cultures. Swelling was completely abolished by co-treatment with MSO, an inhibitor of glutamine synthetase. We also established that many of the effects caused by ammonia, including the reduction in K+ uptake, increase in Cl- uptake and reduction in myo-inositol uptake were diminished by co-treatment with MSO. Agonists of the peripheral-type BZD receptor aggravated ammonia-induced swelling, whereas a peripheral BZD receptor blocker, PK 11195, diminished the extent of swelling. Our findings implicate glutamine and the peripheral-type benzodiazepine receptor in the pathogenesis of the edema associated with fulminant hepatic failure.

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肝衰竭的星形胶质细胞肿胀:谷氨酰胺和苯二氮卓类药物的作用。
我们研究了蛋氨酸亚砜胺(MSO)和外周苯二氮卓(BZD)配体对氨诱导的星形胶质细胞培养肿胀的影响。与谷氨酰胺合成酶抑制剂MSO共处理可完全消除肿胀。我们还确定了氨引起的许多影响,包括K+摄取的减少,Cl-摄取的增加和肌醇摄取的减少,通过与MSO共同处理而减少。外周型BZD受体激动剂加重氨诱导的肿胀,而外周型BZD受体阻滞剂PK 11195减轻肿胀程度。我们的研究结果提示谷氨酰胺和外周型苯二氮卓受体参与暴发性肝衰竭相关水肿的发病机制。
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Monitoring of Cerebral Blood Flow and Metabolism in Intensive Care Molecular biology of blood-brain barrier ontogenesis and function. Astrocyte swelling in liver failure: role of glutamine and benzodiazepines. Temporal profiles of Ca2+/calmodulin-dependent and -independent nitric oxide synthase activity in the rat brain microvessels following cerebral ischemia. The effect of BAY K-8644 on cytotoxic edema induced by total ischemia of rat brain.
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