Abstract
Recent investigations from our laboratories have identified N‐acetylaspartylglutamate (NAAG) as the probable primary axon‐to‐glia signalling agent and source of signalling glutamate (GLU) at nonsynaptic regions of crayfish nerve fibers. NAAG is released from giant axons and mimics the action of the natural signalling agent in hyperpolarizing the glia. GLU formed extracellularly during inactivation of NAAG by NAALADase has a similar, but smaller, effect on the glia. A consequence of these actions of NAAG and GLU appears to be an activation of a signal transduction cascade leading to modulation of water and K+ homeostasis of the neuronal microenvironment. GLU or a related substance also appears to be a neuron‐glia signalling agent at nonsynaptic and synaptic regions of vertebrate nervous system. Therefore, conserved mechanisms of neuron‐glia signalling, mediated at least in part by NAAG and/or GLU, may regulate signal transmission and processing at axons and synapses under physiological and pathological conditions in invertebrates and vertebrates.Acknowledgements: Supported by NIH grant NS34799 and Guilford Pharmaceuticals (Baltimore, MD).
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