Glutamate receptor-induced cyclic GMP formation in primary cultures of mesencephalic neurons.

The link between excitatory amino acid (EAA) receptor activation and the nitric oxide/cyclic GMP intracellular pathway was investigated in primary cultures of mouse mesencephalic neurons. L-glutamate, N-methyl-D-aspartate (NMDA), kainate (KA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate were able to induce cyclic GMP formation. NMDA and KA were the most effective and their action could be blocked, besides the specific antagonists 2-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione, by NG-nitro-L-arginine, a nitric oxide synthase inhibitor. This finding demonstrates that nitric oxide generation is necessary for EAA-induced cyclic GMP formation and provides indirect evidence for nitric oxide synthase activity in mesencephalic neurons. GMP increase induced by NMDA or KA was potentiated by carbachol or by exogenous activation of protein kinase C with phorbol esters. A clarification of the early intracellular events that follow EAA receptor activation may be important for understanding the physiological and excitotoxic events linked to these receptors in the mesencephalon.