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Handbook of Neurochemistry and Molecular Neurobiology pp 361–374Cite as

P2 Purinergic Receptor

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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 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 P2X4 and P2Y6 receptors, respectively. Molecular-, cellular-, and system-level evidences for extracellular nucleotide signaling place P2 purinergic receptors in the central stage in the function of CNS.

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Abbreviations

αβmeATP:

α,β-methylene ATP

2-MeSADP:

2-methylthio-ADP

adBDNF:

BDNF-transducing recombinant adenovirus

anti-TrkB:

antibody against the TrkB receptor

BDNF siRNA:

short interfering RNA directed against BDNF

CNS:

central nervous system

ERK:

extracellular signal regulated protein kinase

IP3 :

inositol trisphosphate

KA:

kainic acid

LI:

lamina I

MAP:

mitogen-activated protein

NMDA:

N-methyl-d-aspartate

PI3K:

phosphatidylinositol 3-kinase

PS:

phosphatidylserine

PTX:

pertussis toxin

TNP-ATP:

2′,3′-O-(2,4,6-trinitrophenyl)-ATP

TrkB–Fc:

BDNF-sequestering fusion protein

UTP:

uridine 5′-triphosphate

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Authors
  1. K. Inoue
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Group Director of Neuro-Developmental Disorder Research Group, RIKEN Brain Science Institute, 351-0198, 2-1 Hirosawa Wako-shi, Saitama, Japan

    Katsuhiko Mikoshiba

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Inoue, K. (2009). P2 Purinergic Receptor. In: Lajtha, A., Mikoshiba, K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30370-3_19

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