GABA and glycine as neurotransmitters: a brief history
GABA and glycine as neurotransmitters: a brief history
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DOI：
10.1038/sj.bjp.0706443
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发表时间：
2006-01-01
影响因子：
7.3
通讯作者：
Smart, TG
中科院分区：
文献类型：
--
作者：
Bowery, NG;Smart, TG
γ-氨基丁酸（GABA）作为一种潜在的重要脑化学物质出现在50多年前，但它作为神经递质的重要性直到16年后才被完全认识到。我们现在知道，哺乳动物大脑中至少有40%的抑制性突触处理使用GABA。确定它作为一种传递器的作用是一个漫长的过程，而且以我们目前的知识，似乎很难相信它在哺乳动物大脑中的作用曾经有过任何争议。我们现在拥有的关于GABA受体的详细信息，以及丰富的促进或减少GABA受体机制的药物，使进一步研究的前景非常令人兴奋。与GABA相比，甘氨酸作为递质的出现似乎相对无痛。也许这是适合最简单的发射机结构！大约40年前，它在脊髓和脑干中被发现，仅仅两年后，就有人提出将其赋予“神经递质”地位。又过了16年，这种受体才被生化分离出来。现在，它被认为是一种重要的脊髓和脊髓上抑制性递质，我们知道许多关于它的分子结构和神经元周围运输的细节。这些受体的药理学落后于GABA。我们已经很容易地将其与GABA受体联系起来，并没有丰富多样的变构调节剂，这为我们提供了一个用于焦虑、失眠、癫痫、麻醉和痉挛的重要药物的虚拟宝库，所有这些都源于简单的中性氨基酸GABA的作用。然而，甘氨酸受体参与运动反射和伤害性途径的认识以及最近出现的表现出某种亚型选择性的药物使得设计甘氨酸受体的选择性治疗配体的目标更加接近。
gamma-Aminobutyric acid (GABA) emerged as a potentially important brain chemical just over 50 years ago, but its significance as a neurotransmitter was not fully realized until over 16 years later. We now know that at least 40% of inhibitory synaptic processing in the mammalian brain uses GABA. Establishing its role as a transmitter was a lengthy process and it seems hard to believe with our current knowledge that there was ever any dispute about its role in the mammalian brain. The detailed information that we now have about the receptors for GABA together with the wealth of agents which facilitate or reduce GABA receptor mechanisms make the prospects for further research very exciting. The emergence of glycine as a transmitter seems relatively painless by comparison to GABA. Perhaps this is appropriate for the simplest of transmitter structures! Its discovery within the spinal cord and brainstem approximately 40 years ago was followed only 2 years later by the proposal that it be conferred with 'neurotransmitter' status. It was another 16 years before the receptor was biochemically isolated. Now it is readily accepted as a vital spinal and supraspinal inhibitory transmitter and we know many details regarding its molecular structure and trafficking around neurones. The pharmacology of these receptors has lagged behind that of GABA. There is not the rich variety of allosteric modulators that we have come to readily associate with GABA receptors and which has provided us with a virtual treasure trove of important drugs used in anxiety, insomnia, epilepsy, anaesthesia, and spasticity, all stemming from the actions of the simple neutral amino acid GABA. Nevertheless, the realization that glycine receptors are involved in motor reflexes and nociceptive pathways together with the more recent advent of drugs that exhibit some subtype selectivity make the goal of designing selective therapeutic ligands for the glycine receptor that much closer.