EXCITATORY AMINO-ACID RESPONSE IN CULTURED RAT STRIATAL NEURONS RESULTS IN A DEVELOPMENTALLY-REGULATED CGMP FORMATION

Glutamate and its analogues play a central role in excitatory neurotra nsmission throughout the brain. Their signal in the postsynaptic cells can be transduced by several second messengers. Here we show that in primary cultures of embryonic rat striatum, excitatory amino acid rece ptor stimulation increases cyclic GMP intracellular concentration and the magnitude of this response depends upon the time in culture. Forma tion of cyclic GMP appears to be mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA type excitatory amino acid receptors, it is block ed by specific excitatory amino acid antagonists and requires extracel lular Ca++. The effect mediated via the NMDA receptor is also regulate d by extracellular Mg++. These results show that excitatory amino acid s make use of cyclic GMP for signal transduction in striatal neurons i n vitro. We suggest that cyclic GMP may be an independent second messe nger possibly important in the development of a defined population of striatal neurons.