NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, increases extracellular GABA in the striatum of the freely moving rat.
We investigated the effect of an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), on the levels of endogenous GABA in the rat striatum using in vivo microdialysis. Rats were perfused with the artificial CSF containing L-NMMA (0.1, 0.3 and 1.0 mM) or its inactive isomer D-NMMA (1.0 mM) for 1 h. Infusion of L-NMMA, but not its D-isomer, dose-dependently increased GABA concentration. Co-infusion with tetrodotoxin (1 microM) did not antagonize the increase of GABA induced by L-NMMA. These results show that decreased NO activity enhances GABA release even in the absence of depolarization of GABA neurones. We conclude that NO may be directly acting on GABA nerve terminals and tonically inhibiting GABA release or synthesis under basal conditions.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D018755:GABA Agonists; D018377:Neurotransmitter Agents; D019323:omega-N-Methylarginine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D019001:Nitric Oxide Synthase