Abstract
The immunocytes microglia in the central nervous system (CNS) were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin (IL)-8 from monocytes and macrocytes. So there raises a question: whether purinoceptor P2Y6 also takes part in neuroinflammation? Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including (1) structure of purinoceptor P2Y6; (2) distribution and properties of purinoceptor P2Y6; (3) relationships between purinoceptor P2Y6 and microglia; (4) relationships between purinoceptor P2Y6 and immunoinflammation. It’s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.
摘要
小胶质细胞是中枢神经系统中的一种免疫活性细胞, 在神经退行性疾病的发生发展中起着重要作用, 近年已经引起基础研究者的高度重视。 嘌呤能受体P2Y6是P2受体家族中的一员, 近年来也引起了科学界的关注。 有研究表明, P2Y6受体在中枢神经系统中介导小胶质细胞的活化及其吞噬作用, 在免疫系统中参与单核巨噬细胞分泌释放细胞因子IL-8。 在中枢神经系统中P2Y6受体是否也参与了炎症因子的产生呢? 本文就以下四个方面对P2Y6受体做一综述:(1)P2Y6受体的结构; (2)P2Y6受体的分布及特性; (3)P2Y6受体与小胶质细胞的关系; (4)P2Y6受体与免疫炎症的关系。 推测P2Y6受体可能在中枢神经系统的免疫炎症反应中起重要作用, 仍需进一步的研究去证实。
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Tu J, Wang LP. Therapeutic potential of extracellular ATP and P2 receptors in nervous system diseases. Neurosci bull 2009, 25: 27–32.
Inoue K. Purinergic systems in microglia. Cell Mol Life Sci 2008, 65: 3074–3080.
Köttgen M, Löffler T, Jacobi C, Nitschke R, Pavenstädt H, Schreiber R, et al. P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport. J Clin Invest 2003, 111: 371–379.
Gendron FP, Chalimoniuk M, Strosznajder J, Shen S, González FA, Weisman GA, et al. P2X7 nucleotide receptor activation enhances IFN gamma-induced type II nitric oxide synthase activity in BV-2 microglial cells. J Neurochem 2003, 87: 344–352.
Schrader AM, Camden JM, Weisman GA. P2Y2 nucleotide receptor up-regulation in submandibular gland cells from the NOD. B10 mouse model of Sjogren’s syndrome. Arch Oral Biol 2005, 50: 533–540.
Weisman GA, Wang M, Kong Q, Chorna NE, Neary JT, Sun GY, et al. Molecular determinants of P2Y2 nucleotide receptor function: implications for proliferative and inflammatory pathways in astrocytes. Mol Neurobiol 2005, 31: 169–183.
Seye CI, Yu N, Jain R, Kong Q, Minor T, Newton J, et al. The P2Y2 nucleotide receptor mediates UTP-induced vascular cell adhesion molecule-1 expression in coronary artery endothelial cells. J Biol Chem 2003, 278: 24960–24965.
North RA, Barnard EA. Nucleotide receptors. Curr Opin Neurobiol 1997, 7: 346–357.
Boarder MR, Turner JT, Erb L, Weisman GA. Classification of P2 purinoceptors. Not all G protein-coupled P2 purinoceptors can be classed as P2Y. Trends Pharmacol Sci 1994, 15: 280–281.
Pidlaoan LV, Jin J, Sandhu AK, Athwal RS, Kunapuli SP. Colocalization of P2Y2 and P2Y6 receptor genes at human chromosome 11q13.3–14.1. Somat Cell Mol Genet 1997, 23: 291–296.
Maier R, Glatz A, Mosbacher J, Bilbe G. Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues. Biochem Biophys Res Commun 1997, 240: 298–302.
Fields RD, Burnstock G. Purinergic signalling in neuron-glia interactions. Nat Rev Neurosci 2006, 7: 423–436.
Chang K, Hanaoka K, Kumada M, Takuwa Y. Molecular cloning and functional analysis of a novel P2 nucleotide receptor. J Biol Chem 1995, 270: 26152–26158.
Von Kugelgen I, Wetter A. Molecular pharmacology of P2Y-receptors. Naunyn Schmiedebergs Arch Pharmacol 2000, 362(4–5): 310–323.
Webb TE, Boluyt MO, Barnard EA. Molecular biology of P2Y purinoceptors: expression in rat heart. J Auton Pharmacol 1996, 16: 303–307.
Southey MC, Hammet F, Hutchins AM, Paidhungat M, Somers GR, Venter DJ. Molecular cloning and sequencing of a novel human P2 nucleotide receptor. Biochim Biophys Acta 1996, 1309: 77–80.
Xiang Z, Burnstock G. Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system. Histochem Cell Biol 2006, 125: 327–336.
Kobayashi K, Fukuoka T, Yamanaka H, Dai Y, Obata K, Tokunaga A, et al. Neurons and glial cells differentially express P2Y receptor mRNAs in the rat dorsal root ganglion and spinal cord. J Comp Neurol 2006, 498: 443–454.
Communi D, Parmentier M, Boeynaems JM. Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochem Biophys Res Commun 1996, 222: 303–308.
Nicholas RA, Lazarowski ER, Watt WC, Li Q, Boyer J, Harden TK. Pharmacological and second messenger signalling selectivities of cloned P2Y receptors. J Auton Pharmacol 1996, 16: 319–323.
Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, et al. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 2007, 446: 1091–1095.
Warny M, Aboudola S, Robson SC, Sévigny J, Communi D, Soltoff SP, et al. P2Y(6) nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide. J Biol Chem 2001, 276: 26051–26056.
Grbic DM, Degagné E, Langlois C, Dupuis AA, Gendron FP. Intestinal inflammation increases the expression of the P2Y6 receptor on epithelial cells and the release of CXC chemokine ligand 8 by UDP. J Immunol 2008, 180: 2659–2668.
Kukulski F, Ben Yebdri F, Lefebvre J, Warny M, Tessier PA, Sevigny J. Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo. J Leukoc Biol 2007, 81: 1269–1275.
Marcet B, Horckmans M, Libert F, Hassid S, Boeynaems JM, Communi D. Extracellular nucleotides regulate CCL20 release from human primary airway epithelial cells, monocytes and monocyte-derived dendritic cells. J Cell Physiol 2007, 211: 716–727.
Bar I, Guns PJ, Metallo J, Cammarata D, Wilkin F, Boeynams JM, et al. Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Mol Pharmacol 2008, 74: 777–784.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Liu, GD., Ding, JQ., Xiao, Q. et al. P2Y6 receptor and immunoinflammation. Neurosci. Bull. 25, 161–164 (2009). https://doi.org/10.1007/s12264-009-0120-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12264-009-0120-3