P2 Purinergic Receptor
Accumulating findings indicate that interactions between extracellular nucleotides and P2 purinergic receptors play important roles in cell-to-cell communication in the central nervous system (CNS), even though ATP is recognized primarily to be a source o
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P2 Purinergic Receptor
K. Inoue
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
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P2 Purinergic Receptor in the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
3 3.1 3.1.1 3.1.2
Structure and Function of P2X Family in Neural Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 P2X4 and Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 The Mechanism of Microglial P2X4-Dependent Neuropathic Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 The Mechanism of P2X4R Upregulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
4 4.1 4.2 4.3
Structure and Function of P2Y Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 P2Y1 and Glio-Transmission in Astrocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 P2Y12 and Microglial Chemotaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 P2Y6 and Microglial Phagocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
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Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
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2009 Springer Science+Business Media, LLC.
362
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P2 purinergic receptor
Abstract: Accumulating findings indicate that interactions between extracellular nucleotides and P2 purinergic receptors play important roles in cell-to-cell communication in the central nervous system (CNS), 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 family) and metabotropic receptors (P2Y family). P2X receptors (seven types; P2X1–P2X7) contain intrinsic pores that open by binding with ATP. P2Y receptors (eight types; P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14) are activated by nucleotides and couple to intracellular second-messenger systems through heteromeric G-proteins. Nucleotides are released or leaked from nonexcitable cells as well as neurons in physiological and pathophysiological conditions. Glia is the interesting nonexcitable cell and is 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 ma
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