Glutamate and its Derivatives in the Regulation of Peripheral Cholinergic Neurotransmission

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Abstract

In the CNS, glutamate is the main excitatory neurotransmitter, while gamma-aminobutyric acid (GABA) functions as the main inhibitory neurotransmitter. N-acetylaspartylglutamate (NAAG), in turn, is the most abundant neuropeptide in the CNS and is also capable of acting as a neurotransmitter. This review analyzes experimental data proving the participation of all three of these signaling molecules in the functioning of the neuromuscular junction, which is a “classical” cholinergic synapse of the peripheral nervous system and, until recently, was considered the most studied synaptic junction in the organism of vertebrates and humans. To date, all three signaling molecules have been identified in the area of the neuromuscular junction, data have been obtained on their release into the synaptic cleft, and receptor proteins have been discovered whose activation affects the processes of both spontaneous and evoked quantal release of acetylcholine. It is noted that in mammalian synapses, glutamate, NAAG and GABA unidirectionally inhibit the process of non-quantal release of acetylcholine. The mechanisms of these modulatory pathways of glutamate and its derivatives signaling are realized with the involvement of all three compartments of the synaptic contact: nerve ending, muscle fiber and perisynaptic Schwann cell.

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About the authors

N. S. Fedorov

Kazan Institute of Biochemistry and Biophysics, RAS

Email: artur57@list.ru
Russian Federation, Kazan

E. S. Nevsky

Kazan Institute of Biochemistry and Biophysics, RAS; Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University

Email: artur57@list.ru
Russian Federation, Kazan; Kazan

A. R. Tokmakova

Kazan Institute of Biochemistry and Biophysics, RAS

Email: artur57@list.ru
Russian Federation, Kazan

A. I. Malomouzh

Kazan Institute of Biochemistry and Biophysics, RAS; Kazan National Research Technical University

Author for correspondence.
Email: artur57@list.ru
Russian Federation, Kazan; Kazan

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2. Fig. 1. Schematic of glutamatergic regulation of acetylcholine release in amphibian and mammalian neuromuscular synapses.

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3. Fig. 2. Schematic representation of data on the role of neuropeptide N-acetylaspartylglutamate (NAAG) in the regulation of acetylcholine release processes in reptilian and mammalian neuromuscular synapses.

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4. Fig. 3. Schematic of GABAergic regulation of acetylcholine release in amphibian and mammalian neuromuscular synapses.

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