Presynaptic NMDA receptors stimulate noradrenaline release in the cerebral cortex.

Previous investigations in our laboratory revealed that N-methyl-D-aspartate (NMDA) and L-glutamate stimulate [3H]noradrenaline release in rat brain cortex slices (Fink et al., 1989; G&hert and Fink, 1989). However, the exact location of the NMDA receptor involved remained unclear. Tetrodotoxin strongly reduced the stimulatory effect of NMDA but failed to completely abolish it. This finding would be compatible with the view that at least some of the NMDA receptors are located on the nerve terminals themselves. However, this hypothesis was not supported by experiments on cortical synaptosomes, in which there was no stimulatory effect of NMDA on [3H]noradrenaline release. The experiments on synaptosomes, like those on slices, were carried out without exogenous glycine. It has become clear in recent years that activation of the glycine site, which is an important component of the NMDA receptor complex, is crucial for the excitability of the latter (Johnson and Ascher, 1987; Keith et al., 1989). Therefore, in the present study, the possibility was examined that, in superfused thin layers of synaptosomes (in contrast to slices), the amount of endogenous glycine available at the glycine recognition site might not be sufficient. In such synaptosome preparations, endogenous compounds are probably washed away so rapidly by the su-