Extracellular adenosine,formed during low level NMDA receptor activation,provides an inhibitory threshold against further NMDA receptor-midiated neurotransmission in the cortex

In the cortex only a few of the available NMDA receptors must be activated to evoke maximal release of adenosine. In fact, maximal adenosine release occurs at 30 μM NMDA, a concentration at which noradrenaline release is only 20% maximal. NMDA-evoked noradrenaline release appears to require the generation of propagated action potentials, while adenosine release does not. Noncompetitive block of NMDA-evoked release of adenosine, but not noradrenaline, can be overcome by increasing NMDA concentrations. The above findings are consistent with the possibility that there are spare receptors for NMDA-evoked adenosine release, but not for nor-adrenaline release. These spare receptors are not due to elevated levels of glycine in the vicinity of those NMDA receptors mediating adenosine release. Functionally, it appears that low level NMDA receptor activation provides a purinergic inhibitory threshold against higher level NMDA receptor mediated processes. This could provide inhibitory tone and selectivity for critical functions, such as learning, memory, and synaptic plasticity in the cortex. © 1993 Wiley-Liss, Inc.