期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 508, 期 1-3, 页码 115-122出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2004.12.008
关键词
NMDA; (N-methyl-D-asparune); NAAG; (N-acetylasparlylglutamate); neuroprotection; GCP II; (glutamate carboxypeptidase II); NAALADase; (N-acetylated-ot-linked acidic dipeptidase); dynorphin A
Glutamate carboxypeptidase (GCP) II (EC 3.4.17.21), which is also known as N-acetylated-alpha-linked acidic dipeptidase (NAALADase), hydrolyses the endogenous acidic dipeptide N-acetylaspartylglutamate (NAAG), yielding N-acetyl-aspartate and glutamate. Inhibition of this enzyme by 2-(phosphonomethyl) pentanedioic acid (2-PMPA) has been shown to protect against ischemic injury to the brain and hypoxic and metabolic injury to neuronal cells in culture, presumably by increasing and decreasing the extracellular concentrations of NAAG and glutamate, respectively. Since both NAAG and GCP II are found in especially high concentrations in the spinal cord, injuries to the spinal cord involving pathophysiological elevations in extracellular glutamate might be particularly responsive to GCP II inhibition. Lumbar subarachnoid injections of dynorphin A in rats cause ischernic spinal cord injury, elevated extracellular glutamate and a persistent hindlimb paralysis that is mediated through excitatory amino acid receptors. We therefore used this injury model to evaluate the protective effects of 2PMPA. When coadministered with dynorphin A, 2-PMPA significantly attenuated the dynorphin A-induced elevations in cerebrospinal fluid glutamate levels and by 24 h postinjection caused significant dose-dependent improvements in motor scores that were associated with marked histopathological improvements. These results indicate that 2-PMPA provides effective protection against excitotoxic spinal cord injury. Published by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据