Wood J D
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Prog Neurobiol. 1975;5(1):77-95. doi: 10.1016/0301-0082(75)90008-8.
The knowledge that GABA is an inhibitory neurotransmitter substance in brain has spurred a prodigious research effort to implicate GABA in the etiology of seizures. Such an involvement for GABA can occur theoretically at either of two levels, at the level of its metabolism or at the level of its functioning. Convulsant agents such as picrotoxin and bicuculline appear to act by impairing the functioning of GABA at the postsynaptic receptor site, but virtually nothing is known about the attendant molecular events although a major expansion of knowledge in this area may be expected within the next decade. In contrast, a vast amount of data has accumulated with respect to changes in GABA metabolism induced by convulsant agents such as the hydrazines, hydrazides, and hyperbaric oxygen. The problem in this case lies in the interpretation of the data. Are the changes in GABA metabolism the cause of the seizures? There is clearly no simple relationship between seizure activity and any single parameter of GABA metabolism, be it the GABA content of the brain, or the rate of uptake of GABA by cellular components, or the activity of the GABA-synthesizing and degrading enzyme systems, GAD and GABA-T respectively. This finding may, however, be illusory since the parameters of GABA metabolism were in most cases measured using preparations from intact brain tissue. Observed changes in the parameters may not accurately reflect events at a critical subcellular location such as the synaptic cleft. Thus there may well be a simple relationship between the concentration of GABA in the synaptic cleft and seizure activity. Unfortunately the limitations of current technology preclude the testing of this possibility. The author has, however, developed an equation on an empirical basis which provides an excellent relationship between the excitable state of the brain and a function of GABA metabolism which incorporates both changes in GABA level and changes in GAD activity. This equation has been used successfully to explain and rationalize previously anomalous results with respect to changes in GABA metabolism associated with the action of both convulsant and anticonvulsant agents. The concept embodied in the equation is that the excitable state of brain is determined primarily by the rate of synthesis of GABA but that reflects changes in the concentration of GABA in the synaptic cleft has been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
γ-氨基丁酸（GABA）是大脑中的一种抑制性神经递质物质，这一认识激发了大量研究工作，试图将GABA与癫痫的病因联系起来。理论上，GABA在癫痫病因中的作用可在两个层面发生，即其代谢层面或功能层面。惊厥剂如印防己毒素和荷包牡丹碱似乎通过损害GABA在突触后受体部位的功能起作用，但尽管预计在未来十年内该领域的知识会有重大扩展，关于随之发生的分子事件却几乎一无所知。相比之下，关于由肼类、酰肼类和高压氧等惊厥剂引起的GABA代谢变化，已经积累了大量数据。在这种情况下，问题在于数据的解释。GABA代谢的变化是癫痫发作的原因吗？癫痫发作活动与GABA代谢的任何单个参数之间显然没有简单的关系，无论是大脑中的GABA含量、细胞成分对GABA的摄取速率，还是分别为GAD和GABA-T的GABA合成和降解酶系统的活性。然而，这一发现可能是虚幻的，因为在大多数情况下，GABA代谢参数是使用完整脑组织的制剂测量的。观察到的参数变化可能无法准确反映关键亚细胞位置（如突触间隙）的事件。因此，突触间隙中GABA的浓度与癫痫发作活动之间很可能存在简单的关系。不幸的是，当前技术的局限性排除了对这种可能性的测试。然而，作者已在经验基础上建立了一个方程，该方程在大脑的兴奋状态与GABA代谢的一个函数之间提供了极好的关系，该函数同时纳入了GABA水平的变化和GAD活性的变化。这个方程已成功用于解释和合理化先前关于与惊厥剂和抗惊厥剂作用相关的GABA代谢变化的异常结果。该方程所体现的概念是，大脑的兴奋状态主要由GABA合成速率决定，但也有人认为这反映了突触间隙中GABA浓度变化。（摘要截取自400字）
