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Interaction between the transmitters ATP and glutamate in the central nervous system
Author(s) -
Illes Peter,
Wirkner Kerstin,
Nörenberg Wolfgang,
Masino Susan A.,
Dunwiddie Thomas V.
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1100
Subject(s) - neuroscience , glutamatergic , glutamate receptor , nmda receptor , excitatory postsynaptic potential , biology , inhibitory postsynaptic potential , postsynaptic potential , chemistry , receptor , biochemistry
Although it has been demonstrated repeatedly that ATP is a fast excitatory transmitter in the central nervous system (CNS), there are only limited data to indicate a corelease of ATP with other transmitters such as γ–aminobutyric acid or noradrenaline. Somewhat surprisingly, there is no evidence hitherto for glutamate‐ATP cotransmission in spite of the widespread distribution of glutamatergic neurons in the brain and spinal cord. However, ATPergic and glutamatergic neurons may interact both at the pre‐ and postsynaptic level. Presynaptic P2X receptors facilitate glutamate release both from the terminals of mesencephalic proprioceptive trigeminal neurons projecting to the motor trigeminal nucleus in the brainstem and from primary afferent fibers onto dorsal horn neurons of the spinal cord. The inhibitory effect of ATP via presynaptic P2Y receptors has been demonstrated convincingly at noradrenergic but not glutamatergic nerve terminals. However, in addition to the direct effects of ATP, adenosine formed by the enzymatic degradation of ATP can inhibit the release of glutamate from the Schaffer collateral‐commissural pathway onto CA1 pyramidal cells of the hippocampus. Similarly, ATP degraded to adenosine may inhibit the N ‐methyl‐ D ‐aspartate (NMDA)‐induced current in the striatopallidal subpopulation of medium spiny neurons via A 2A receptor activation. Finally, ATP may potentiate the NMDA receptor–mediated depolarization or the underlying inward current at layer V pyramidal neurons of the prefrontal cortex, and P2Y receptors have been suggested to mediate this interaction. Thus, although as a transmitter ATP alters the membrane potential of a limited subset of CNS neurons, it may have widespread and pronounced effects by modulating glutamatergic mechanisms. Drug Dev. Res. 52:76–82, 2001. © 2001 Wiley‐Liss, Inc.