Abstract
Potent actions of ATP in the central nervous system (CNS) were reported in the late 1940’s, but cloning and characterisation of receptors for purines and pyrimidines did not take place until the early 1990’s, which identified seven P2X ion channel receptor subtypes, three of which form the cation channel as homomultimers or heteromultimers. P2X receptor subtypes are widely expressed in the CNS and their distribution is described in different regions. They function in synaptic cotransmission and neuromodulation, as well as in trophic signalling. ATP released from nerves and astroglial cells are predominantly involved in neuron-glial interactions. Purinergic signalling is involved in normal behaviour, including learning and memory, sleep and arousal, locomotor and feeding activities and cognition. P2X receptors participate in CNS pathophysiology, including injury, inflammation, Alzheimer’s and Parkinson’s diseases, multiple sclerosis and amyotrophic lateral sclerosis, depression and anxiety. P2X4 and P2X7 receptor antagonists are effective via microglia against neuropathic pain, while P2X3 receptor antagonists also reduce neuropathic pain, but via a differernt mechanism.
Keywords: ATP, brain stem, glia, glutamate, hippocampus, memory, neurodegenerative diseases, neuropathic pain, neuroprotection, spinal cord.
Current Medicinal Chemistry
Title:Physiopathological Roles of P2X Receptors in the Central Nervous System
Volume: 22 Issue: 7
Author(s): G. Burnstock
Affiliation:
Keywords: ATP, brain stem, glia, glutamate, hippocampus, memory, neurodegenerative diseases, neuropathic pain, neuroprotection, spinal cord.
Abstract: Potent actions of ATP in the central nervous system (CNS) were reported in the late 1940’s, but cloning and characterisation of receptors for purines and pyrimidines did not take place until the early 1990’s, which identified seven P2X ion channel receptor subtypes, three of which form the cation channel as homomultimers or heteromultimers. P2X receptor subtypes are widely expressed in the CNS and their distribution is described in different regions. They function in synaptic cotransmission and neuromodulation, as well as in trophic signalling. ATP released from nerves and astroglial cells are predominantly involved in neuron-glial interactions. Purinergic signalling is involved in normal behaviour, including learning and memory, sleep and arousal, locomotor and feeding activities and cognition. P2X receptors participate in CNS pathophysiology, including injury, inflammation, Alzheimer’s and Parkinson’s diseases, multiple sclerosis and amyotrophic lateral sclerosis, depression and anxiety. P2X4 and P2X7 receptor antagonists are effective via microglia against neuropathic pain, while P2X3 receptor antagonists also reduce neuropathic pain, but via a differernt mechanism.
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Cite this article as:
Burnstock G., Physiopathological Roles of P2X Receptors in the Central Nervous System, Current Medicinal Chemistry 2015; 22 (7) . https://dx.doi.org/10.2174/0929867321666140706130415
DOI https://dx.doi.org/10.2174/0929867321666140706130415 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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