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The role of nucleotides in the neuron–glia communication responsible for the brain functions
Author(s) -
Inoue Kazuhide,
Koizumi Schuichi,
Tsuda Makoto
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04824.x
Subject(s) - purinergic receptor , p2y receptor , microglia , metabotropic receptor , receptor , biology , microbiology and biotechnology , ionotropic effect , neuroglia , intracellular , nucleotide , cell signaling , extracellular , neuroscience , signal transduction , biochemistry , glutamate receptor , central nervous system , inflammation , immunology , gene
Abstract Accumulating findings indicate that nucleotides play an important role in cell‐to‐cell communication through P2 purinoceptors, even though ATP is recognized primarily to be a source of free energy and nucleotides are key molecules in cells. P2 purinoceptors are divided into two families, ionotropic receptors (P2X) and metabotropic receptors (P2Y). P2X receptors (7 types; P2X 1 –P2X 7 ) contain intrinsic pores that open by binding with ATP. P2Y (8 types; P2Y 1, 2, 4, 6, 11, 12, 13, and 14 ) are activated by nucleotides and couple to intracellular second‐messenger systems through heteromeric G‐proteins. Nucleotides are released or leaked from non‐excitable cells as well as neurons in physiological and pathophysiological conditions. One of the most exciting cells in non‐excitable cells is the glia cells, which are classified into astrocytes, oligodendrocytes, and microglia. Astrocytes express many types of P2 purinoceptors and release the ‘gliotransmitter’ ATP to communicate with neurons, microglia and the vascular walls of capillaries. Microglia also express many types of P2 purinoceptors and are known as resident macrophages in the CNS. ATP and other nucleotides work as ‘warning molecules’ especially through activating microglia in pathophysiological conditions. Microglia play a key role in neuropathic pain and show phagocytosis through nucleotide‐evoked activation of P2X 4 and P2Y 6 receptors, respectively. Such strong molecular, cellular and system‐level evidence for extracellular nucleotide signaling places nucleotides in the central stage of cell communications in glia/CNS.