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Abstract <p>Glutamate is the master excitatory neurotransmitter in thecentral nervous system, while gamma-aminobutyric acid (GABA), produceddue to glutamate decarboxylation, functions as the master inhibitoryneurotransmitter. <i>N</i>-acetylaspartylglutamate(NAAG), the most abundant neuropeptide in the CNS, is also capableof acting as a neurotransmitter. This review addresses experimentaldata that prove the involvement of all these three signaling moleculesin the functioning of a neuromuscular junction, a classical cholinergicsynapse in the peripheral nervous system that has been consideredto be the most studied in the organism of vertebrates and humansuntil recently. To date, all three signaling molecules have beenfound at the neuromuscular junction and shown to release into thesynaptic cleft. Moreover, there have been identified receptor proteinswhose activation influences both spontaneous and evoked quantalacetylcholine release. Notably, glutamate, NAAG and GABA inhibitnon-quantal acetylcholine release in mammalian synapses. The mechanismsof these modulatory signaling pathways of glutamate and its derivativesare implemented due to cooperation of all three compartments ofthe neuromuscular junction: nerve ending, muscle fiber, and perisynapticSchwann cell.</p>

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Glutamate and Its Derivatives in Regulation of Peripheral Cholinergic Neurotransmission

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • N. S. Fedorov,
  • E. S. Nevsky,
  • A. R. Tokmakova,
  • A. I. Malomouzh

摘要

Abstract

Glutamate is the master excitatory neurotransmitter in thecentral nervous system, while gamma-aminobutyric acid (GABA), produceddue to glutamate decarboxylation, functions as the master inhibitoryneurotransmitter. N-acetylaspartylglutamate(NAAG), the most abundant neuropeptide in the CNS, is also capableof acting as a neurotransmitter. This review addresses experimentaldata that prove the involvement of all these three signaling moleculesin the functioning of a neuromuscular junction, a classical cholinergicsynapse in the peripheral nervous system that has been consideredto be the most studied in the organism of vertebrates and humansuntil recently. To date, all three signaling molecules have beenfound at the neuromuscular junction and shown to release into thesynaptic cleft. Moreover, there have been identified receptor proteinswhose activation influences both spontaneous and evoked quantalacetylcholine release. Notably, glutamate, NAAG and GABA inhibitnon-quantal acetylcholine release in mammalian synapses. The mechanismsof these modulatory signaling pathways of glutamate and its derivativesare implemented due to cooperation of all three compartments ofthe neuromuscular junction: nerve ending, muscle fiber, and perisynapticSchwann cell.