| Nitric Oxide
Synthase Inhibition and Glutamate Binding in
Quinolinate-Lesioned Rat Hippocampus
V.
LISÝ, F. ŠŤASTNÝ1
Institute
of Physiology, Academy of Sciences of the Czech
Republic, and 1Prague
Psychiatric Center, Prague, Czech Republic
Received August 2, 2001
Accepted November 30, 2001
Summary
The effect of lesions induced by
bilateral intracerebroventricular (ICV) 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
NG-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)-[1,2-3H]-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.
.
Key
words
Quinolinic
acid · NMDA receptor · Membrane binding ·
Nitric oxide synthase (NOS) · Neurodegeneration
Reprint
requests
Dr.Václav Lisý, Institute of Physiology,
Academy of Sciences, Vídeňská 1083, 142 20
Prague 4, Czech Republic, Phone: (420-2)475-2542,
Fax: (420-2)475-2488, E-mail: lisy@biomed.cas.cz
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