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 neurotransmission 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 receptor stimulation increases cyclic GMP intracellular concentration and the magnitude of this response depends upon the time in culture. Formation of cyclic GMP appears to be mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA type excitatory amino acid receptors, it is blocked by specific excitatory amino acid antagonists and requires extracellular Ca++. The effect mediated via the NMDA receptor is also regulated by extracellular Mg++. These results show that excitatory amino acids make use of cyclic GMP for signal transduction in striatal neurons in vitro. We suggest that cyclic GMP may be an independent second messenger possibly important in the development of a defined population of striatal neurons.