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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Neuronal P2 Receptors of the Central Nervous System

Author(s): Peter Illes and Joaquim A. Ribeiro

Volume 4, Issue 8, 2004

Page: [831 - 838] Pages: 8

DOI: 10.2174/1568026043451032

Price: $65


Neurons of the central nervous system (CNS) are endowed with ATP-sensitive receptors belonging to the P2X (multimeric ligand-gated cationic channels) and P2Y (G protein-coupled 7TM receptors) types. To date seven P2X and eight P2Y receptors of human origin have been molecularly identified and functionally characterized. P2X subunits may occur as homooligomers or as heterooligomeric assemblies of more than one subunit. P2X7 subunits do not form heterooligomeric assemblies and are uniqe in mediating apoptosis and necrosis of glial cells and possibly also of neurons. The P2X2, P2X4, P2X4 / P2X6 and P2Y1 receptors appear to be the predominant neuronal types. Whereas a number of P2X receptors mediate fast synaptic responses to the transmitter ATP, P2Y receptors mediate either slow changes of the membrane potential in response to non-synaptically released ATP or the interaction with receptors for other transmitters. The localisation of these receptors may be at the terminal axons (presynaptic) or at the somato-dendritic region (postsynaptic). Whereas presynaptic P2 receptors may be either excitatory (P2X) or inhibitory (P2Y), postsynaptic P2 receptors appear to be without exception excitatory. Finally, the enzymatic degradation of ATP may lead to the local generation of adenosine which can modulate ATP-related neurotransmission via activation of A1 or A2A receptors.

Keywords: neuronal p2 receptors, ligand-gated cationic channels, heterooligomeric assemblies, a2a receptors

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