Interaction between the transmitters ATP and glutamate in the central nervous system

Although it has been demonstrated repeatedly that, ATP is a fast excitatory transmitter in the central nervous system (CNS), there are only limited da ta to indicate a corelease of ATP with other transmitters such as gamma -am inobutyric acid or noradrenaline. Somewhat surprisingly, there is no eviden ce hitherto for glutamate-ATP cotransmission in spite of the widespread dis tribution of glutamatergic neurons in the brain and spinal cord. However, A TPergic and glutamatergic neurons may interact both at the pre- and postsyn aptic level. Presynaptic P2X receptors facilitate glutamate release both fr om the terminals of mesencephalic proprioceptive trigeminal neurons project ing to the motor trigeminal nucleus in the brainstem and from primary affer ent fibers onto dorsal horn neurons of the spinal cord. The inhibitory effe ct of ATP via presynaptic P2Y receptors has been demonstrated convincingly at noradrenergic but not glutamatergic nerve terminals. However, in additio n to the direct effects of ATP adenosine formed by the enzymatic degradatio n 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)-induc ed current in the striatopallidal subpopulation of medium spiny neurons via A(2A) receptor activation. Finally, ATP may potentiate the NMDA receptor-m ediated depolarization or the underlying inward current at layer V pyramida l neurons of the prefrontal cortex, and P2Y receptors have been suggested t o mediate this interaction. Thus, although as a transmitter ATP alters the membrane potential of a limited subset of CNS neurons, it may have widespre ad and pronounced effects by modulating glutamatergic mechanisms. Drug Dev. Res. 52:76-82, 2001. (C) 2001 Wiley-Liss, Inc.