對神經細胞之間訊息的聯繫而言，神經傳遞物質釋放是一個相當重要且複雜的過程。適當的神經傳遞物質釋放對神經系統維持正常功能是必須的，但是過度釋放,特別是一種興奮性神經傳遞物質glutamate，對神經細胞會產生毒殺的作用，許多研究證據指出中樞神經系統的退化及病變大致和glutamate 有著密切相關性。因此，glutamate在神經突觸間隙的量和神經功能的維持有相當的關聯性。最近有研究指出glutamate 從神經末梢的釋放可以被許多突觸前接受器所調節特別是G protein-coupled receptors，而這些接受器的活化對神經傳遞物質glutamate的釋放會產生抑制或是促進之作用，同時接受器彼此之間的功能也會互相影響，如此一個突觸前調節作用或許有助於去調整神經細胞間傳遞作用的強度而避免過多的神經傳遞物質glutamate 被釋放出來。因此，從神經生理的觀點來看這些突觸前接受器可能在presynaptic plasticity 上扮演一個相當重要的角色， 而從藥理的角度來看這些突觸前接受器似乎可以發展作為一些臨床治療藥物作用的標器；本篇文章將針對Gs protein-coupled -adrenoreceptor 和Gi/o proteincoupled5-HT1A receptor 對神經傳遞物質glutamate 釋放過程的調控作用及其交互作用之機轉做一個討論。

Glutamate is one of the excitatory neurotransmitters in the CNS and exists in very highconcentrations in the brain. Proper glutamate release is required for normal neuronal function suchas learning and memory formation or plasticity of the brain, but abnormal glutamate release hasbeen implicated in a number of neuropathological conditions ranging from acute insults such asstroke to chronic neurodegenerative disorders such as Alzheimer's disease. Thus, the amount ofglutamate in the synaptic cleft is associated with themaintenance of neuronal functions. Recently,the regulation of glutamate release from presynaptic terminals by a variety of presynapticreceptors, especiallyG protein-coupled receptors (GPCRs), has been reported. Activation of theseGPCRs has been shown to produce opposing effects on glutamate release, as well as crossregulatingeach other's function within the same terminals. Such presynaptic modulation mighthelp shape the strength of synaptic transmission at glutamatergic synapses. Therefore, thesepresynaptic receptors are of considerable importance both from the neurophysiological point ofview and also as potential targets for therapeutic agents. In this article, the effects of modulationof glutamate release by Gs protein-coupled -adrenoreceptors and Gi/o protein-coupled 5-HT1Areceptors, and presynaptic interactions between these receptors modulating glutamate releasefrom nerve terminals are discussed.