Roles of P2 receptors in glial cells: focus on astrocytes
- PMID: 18404462
- PMCID: PMC2096663
- DOI: 10.1007/s11302-006-9016-0
Roles of P2 receptors in glial cells: focus on astrocytes
Abstract
Central nervous system glial cells release and respond to nucleotides under both physiological and pathological conditions, suggesting that these molecules play key roles in both normal brain function and in repair after damage. In particular, ATP released from astrocytes activates P2 receptors on astrocytes and other brain cells, allowing a form of homotypic and heterotypic signalling, which also involves microglia, neurons and oligodendrocytes. Multiple P2X and P2Y receptors are expressed by both astrocytes and microglia; however, these receptors are differentially recruited by nucleotides, depending upon specific pathophysiological conditions, and also mediate the long-term trophic changes of these cells during inflammatory gliosis. In astrocytes, P2-receptor-induced gliosis occurs via activation of the extracellular-regulated kinases (ERK) and protein kinase B/Akt pathways and involves induction of inflammatory and anti-inflammatory genes, cyclins, adhesion and antiapoptotic molecules. While astrocytic P2Y₁ and P2Y(₂,₄) are primarily involved in short-term calcium-dependent signalling, multiple P2 receptor subtypes seem to cooperate to astrocytic long-term changes. Conversely, in microglia, exposure to inflammatory and immunological stimuli results in differential functional changes of distinct P2 receptors, suggesting highly specific roles in acquisition of the activated phenotype. We believe that nucleotide-induced activation of astrocytes and microglia may originally start as a defence mechanism to protect neurons from cytotoxic and ischaemic insults; dysregulation of this process in chronic inflammatory diseases eventually results in neuronal cell damage and loss. On this basis, full elucidation of the specific roles of P2 receptors in these cells may help exploit the beneficial neuroprotective features of activated glia while attenuating their harmful properties and thus provide the basis for novel neuroprotective strategies that specifically target the purinergic system.
Figures
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2096663/bin/11302_2006_Article_9016_Fig2.gif)
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/2096663/bin/11302_2006_Article_9016_Fig1.gif)
Similar articles
-
Pathophysiological roles of P2 receptors in glial cells.Novartis Found Symp. 2006;276:91-103; discussion 103-12, 275-81. Novartis Found Symp. 2006. PMID: 16805425 Review.
-
P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system.Eur J Pharmacol. 2002 Jul 5;447(2-3):247-60. doi: 10.1016/s0014-2999(02)01756-9. Eur J Pharmacol. 2002. PMID: 12151016 Review.
-
P2 receptor signalling, proliferation of astrocytes, and expression of molecules involved in cell-cell interactions.Novartis Found Symp. 2006;276:131-43; discussion 143-7, 233-7, 275-81. Novartis Found Symp. 2006. PMID: 16805427 Review.
-
Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia.Brain Res Brain Res Rev. 2005 Apr;48(2):144-56. doi: 10.1016/j.brainresrev.2004.12.004. Epub 2005 Jan 22. Brain Res Brain Res Rev. 2005. PMID: 15850653
-
P2 receptor signaling in neurons and glial cells of the central nervous system.Adv Pharmacol. 2011;61:441-93. doi: 10.1016/B978-0-12-385526-8.00014-X. Adv Pharmacol. 2011. PMID: 21586367 Review.
Cited by
-
The role of Pannexin-1 channels, ATP, and purinergic receptors in the pathogenesis of HIV and SARS-CoV-2.Curr Opin Pharmacol. 2023 Dec;73:102404. doi: 10.1016/j.coph.2023.102404. Epub 2023 Sep 19. Curr Opin Pharmacol. 2023. PMID: 37734241 Review.
-
Neuron-astrocyte omnidirectional signaling in neurological health and disease.Front Mol Neurosci. 2023 Jun 8;16:1169320. doi: 10.3389/fnmol.2023.1169320. eCollection 2023. Front Mol Neurosci. 2023. PMID: 37363320 Free PMC article. Review.
-
Altered Purinergic Signaling in Neurodevelopmental Disorders: Focus on P2 Receptors.Biomolecules. 2023 May 18;13(5):856. doi: 10.3390/biom13050856. Biomolecules. 2023. PMID: 37238724 Free PMC article. Review.
-
The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain.Cells. 2023 Mar 22;12(6):965. doi: 10.3390/cells12060965. Cells. 2023. PMID: 36980304 Free PMC article. Review.
-
Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data.Front Mol Neurosci. 2023 Feb 3;16:1089871. doi: 10.3389/fnmol.2023.1089871. eCollection 2023. Front Mol Neurosci. 2023. PMID: 36818658 Free PMC article.
References
-
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.2174/1568026043451032', 'is_inner': False, 'url': 'https://doi.org/10.2174/1568026043451032'}, {'type': 'PubMed', 'value': '15078214', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15078214/'}]}
- Illes P, Ribeiro JA (2004) Neuronal P2 receptors of the central nervous system. Curr Top Med Chem 4:831′38 - PubMed
-
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/0163-7258(94)00048-4', 'is_inner': False, 'url': 'https://doi.org/10.1016/0163-7258(94)00048-4'}, {'type': 'PubMed', 'value': '7724657', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/7724657/'}]}
- Abbracchio MP, Burnstock G (1994) Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther 64:445′75 - PubMed
-
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '11171941', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11171941/'}]}
- Khakh BS, Burnstock G, Kennedy C et al (2001) International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53:107′18 - PubMed
-
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/S0165-6147(02)00038-X', 'is_inner': False, 'url': 'https://doi.org/10.1016/s0165-6147(02)00038-x'}, {'type': 'PMC', 'value': 'PMC8653507', 'is_inner': False, 'url': 'http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8653507/'}, {'type': 'PubMed', 'value': '12559763', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/12559763/'}]}
- Abbracchio MP, Boeynaems JM, Barnard EA et al (2003) Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci 24:52′5 - PMC - PubMed
-
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1385/MN:31:1-3:169', 'is_inner': False, 'url': 'https://doi.org/10.1385/mn:31:1-3:169'}, {'type': 'PubMed', 'value': '15953819', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15953819/'}]}
- Weisman GA, Wang M, Kong Q et al (2005) Molecular determinants of P2Y2 nucleotide receptor function: implications for proliferative and inflammatory pathways in astrocytes. Mol Neurobiol 31:169′83 - PubMed
LinkOut - more resources
Full Text Sources
Miscellaneous