The neurotransmitter N-acetylaspartylglutamate in models of pain, ALS, diabetic neuropathy, CNS injury and schizophrenia.

N-Acetylaspartylglutamate (NAAG) is the most abundant and widely distributed peptide transmitter in the mammalian nervous system. NAAG activates the metabotropic glutamate mGlu(3) receptor at presynaptic sites, inhibiting the release of neurotransmitters, including glutamate, and activates mGlu(3) receptors on glial cells, stimulating the release of neuroprotective growth factors from these cells. Elevated levels of glutamate released from neurons are associated with the pathology of stroke, traumatic nervous system injury, amyotrophic lateral sclerosis, inflammatory and neuropathic pain, diabetic neuropathy and the schizophrenia-like symptoms elicited by phencyclidine.

Biosynthesis of NAAG by an enzyme-mediated process in rat central nervous system neurons and glia.

The peptide transmitter N-acetylaspartylglutamate (NAAG) is present in millimolar concentrations in mammalian spinal cord. Data from the rat peripheral nervous system suggest that this peptide is synthesized enzymatically, a process that would be unique for mammalian neuropeptides. To test this hypothesis in the mammalian CNS, rat spinal cords were acutely isolated and used to study the incorporation of radiolabeled amino acids into NAAG.