EFFECTS OF NITRIC-OXIDE SYNTHASE GENE KNOCKOUT ON NEUROTRANSMITTER RELEASE IN-VIVO

Nitric oxide serves as a diffusible messenger within the neuronal netw orks of the brain, Recent studies have suggested that nitric oxide may amplify neurotransmitter release via its ability to diffuse in a retr ograde manner from postsynaptic to presynaptic neurons, Two isoforms o f nitric oxide synthase may be present in neurons: Type I nitric oxide synthase (neuronal isoform) and Type III nitric oxide synthase (endot helial isoform). In this study, we examined the role of nitric oxide a s an amplifier of neurotransmitter release by using K+ and N-methyl-D- aspartate stimulations via microdialysis probes located in cortex, str iatum, and hippocampus, We compared responses obtained in wild-type mi ce versus knockout mice deficient in either neuronal isoform of nitric oxide synthase or endothelial isoform of nitric oxide synthase gene e xpression. No significant differences in glutamate and GABA release we re observed between knockout mice and wild-type mice after K+ stimulat ions. In contrast, N-methyl-D-aspartate-stimulated glutamate release i n cortex was significantly reduced in the neuronal NOS knockout mice, and N-methyl-D-aspartate-stimulated GABA release was significantly red uced in all brain regions of endothelial NOS knockout mice. These data suggest that the two nitric oxide synthase isoforms, most likely due to their specific neuronal localizations, may serve different roles in the modulation of excitatory versus inhibitory neurotransmission in m ammalian brain, (C) 1998 IBRO, Published by Elsevier Science Ltd.