Physiopathological Roles of P2X Receptors in the Central Nervous System
Affiliation: University College Medical School, United Kingdom.
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,
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