Possible involvement of nitric oxide in NMDA-induced glutamate release in the rat striatum: an in vivo microdialysis study.
The involvement of nitric oxide (NO) production in the release of striatal glutamate induced by local infusion of N-methyl-D-aspartate (NMDA) was investigated using microdialysis in freely moving rats. At concentrations of 0.1, 0.25, 0.5 or 1 mM NMDA induced concentration-dependent increases in striatal glutamate release. This effect of NMDA (0.5 mM) was significantly inhibited by tetrodotoxin (10 microM), by striatal perfusion with Ca2+-free medium containing EGTA (5 mM), or by the putative antagonist of intracellular Ca2+, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) (1, 10 or 100 microM). Local infusion of the competitive inhibitors of NO synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) or N(G)-monomethyl-L-arginine (L-NMMA) (both at concentrations 0.1, 0.25, 0.5 or 1 mM) caused the concentration-dependent inhibition of the glutamate response to 0.5 mM NMDA. This effect of NOS inhibition was stereospecific, inasmuch as N(G)-nitro-D-arginine methyl ester (D-NAME) (0.5 or 1 mM) failed to affect NMDA-induced glutamate release. These findings suggest that increased NO production following NMDA receptor activation mediates the increase in release of neurotransmitter glutamate triggered by activation of striatal NMDA receptors.
Bogdanov
M B
MB
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02142, USA.
Wurtman
R J
RJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D009764:o-Phthalaldehyde; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D009764:o-Phthalaldehyde; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester