title: Nitric oxide synthase inhibition and glutamate binding in quinolinate-lesioned rat hippocampus.
abstract: The effect of lesions induced by bilateral intracerebroventricular (i.c.v.) injection of quinolinate (250 nmol of QUIN/ventricle), a selective N-methyl-D-aspartate (NMDA) receptor agonist, on [3H]glutamate ([3H]Glu) binding to the main types of both ionotropic and metabotropic glutamate receptors (iGluR and mGluR) was investigated in synaptic membrane preparations from the hippocampi of 50-day-old rats. The membranes from QUIN injured brains revealed significantly lowered binding in iGluR (by 31%) as well as in mGluR (by 22%) as compared to the controls. Using selected glutamate receptor agonists as displacers of [3H]Glu binding we found that both the NMDA-subtype of iGluR and group I of mGluR are involved in this decrease of binding. Suppression of nitric oxide (NO) production by N(G)-nitro-L-arginine (50 nmol of NARG/ventricle) or the increase of NO generation by 3-morpholinylsydnoneimine (5 nmol of SIN-1/ventricle) failed to alter [3H]Glu or [3H]CPP (3-((D)-2-carboxypiperazin-4-yl)-[1,2-(3)H]-propyl-1-phosphonic acid; NMDA-antagonist) binding declines caused by QUIN-lesions. Thus, our findings indicate that both the NMDA-subtype of iGluR and group I of mGluR are susceptible to the QUIN-induced neurodegeneration in the rat hippocampus. However, the inhibition of NO synthesis did not reveal any protective action in the QUIN-evoked, NMDA-receptor mediated decrease of [3H]Glu binding. Therefore, the additional mechanisms of QUIN action, different from direct NMDA receptor activation/NO production (e.g. lipid peroxidation induced by QUIN-Fe-complexes) cannot be excluded.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague. lisy@biomed.cas.cz
authors.forename: V
authors.initials: V
authors.lastname: Lisý
authors.forename: F
authors.initials: F
authors.lastname: Stastný
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D017378:Quinolinic Acid; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D020030:Nitric Oxide Donors; D014316:Tritium; D019335:Nitroarginine; D018698:Glutamic Acid; C002385:linsidomine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D017378:Quinolinic Acid; D007608:Kainic Acid