Maitre M, Mandel P
C R Acad Sci III. 1984;298(12):341-5.
gamma-Hydroxybutyrate (GHB) fulfills the main criteria of a neurotransmitter: it is unevenly distributed in C.N.S.; it is synthesized from succinic semi-aldehyde by a specific semi-aldehyde succinic reductase localized in neurons, in some dendrites and synaptic terminals; GHB is released by tissue slice depolarization, this release being reduced by 50-60% in a Ca++ free medium. Tetrodotoxin and verapamil strongly inhibited the depolarization evoked-release; high affinity heterogenously distributed binding sites for gamma-hydroxybutyrate exist in the brain. This binding does not require Na+. The bound gamma-hydroxybutyric acid is not displaceable by GABA or GABA agonists. Binding sites are enriched in the synaptosomal fraction; after micro-iontophoretic application, GHB exerts a depressant action on nigral and neocortical cells which is resistant to the presence of bicuculline methiodide. In neuronal cultures, GHB causes a hyperpolarization similar to that produced by GABA; high affinity uptake system for GHB exists both in purified plasma membrane vesicles and in brain tissue slices. This uptake is dependent on an Na+ gradient and is inhibited by ouabaïn and dinitrophenol; GABA does not modify GHB uptake by rat brain slices; GABA derived GHB has a turnover time almost three times faster than that of whole brain serotonin, 6-8 times as rapid as that of whole brain dopamine and 13-19 times as rapid as that of whole brain norepinephrine.
γ-羟基丁酸（GHB）符合神经递质的主要标准：它在中枢神经系统中分布不均；它由琥珀酸半醛通过定位于神经元、某些树突和突触终末的特定半醛琥珀酸还原酶合成；GHB通过组织切片去极化释放，在无Ca++的培养基中这种释放减少50 - 60%。河豚毒素和维拉帕米强烈抑制去极化诱发的释放；大脑中存在对γ-羟基丁酸具有高亲和力的异质性分布结合位点。这种结合不需要Na+。结合的γ-羟基丁酸不能被GABA或GABA激动剂取代。结合位点在突触体部分富集；微量离子电泳应用后，GHB对黑质和新皮质细胞发挥抑制作用，该作用对甲基碘化荷包牡丹碱的存在具有抗性。在神经元培养物中，GHB引起类似于GABA产生的超极化；在纯化的质膜囊泡和脑组织切片中均存在GHB的高亲和力摄取系统。这种摄取依赖于Na+梯度，并被哇巴因和二硝基苯酚抑制；GABA不改变大鼠脑切片对GHB的摄取；源自GABA的GHB的周转时间几乎比全脑血清素快三倍，比全脑多巴胺快6 - 8倍，比全脑去甲肾上腺素快13 - 19倍。
