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Nitric oxide responsible for NMDA receptor-evoked inhibition of arachidonic acid incorporation into lipids of brain membrane

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Molecular and Chemical Neuropathology

Abstract

The activation of the glutamatergic NMDA receptor has no effect on arachidonic acid release from cortical synaptoneurosomal lipids prelabeled with [1-14C]arachidonic acid ([14C]AA). However, activation of NMDA receptor leads to the reduction of AA incorporation into rat brain cortex synaptoneurosomal membrane phosphatidylinositol (PI). The competitive NMDA receptor antagonist, 2-amino-5-phosphovaleric acid (APV), completely eliminates the effect of NMDA on this process. More precise analysis of the sequence of events leading to NMDA-induced decrease of AA incorporation indicates that this process is significantly blocked by voltage-gated sodium and calcium channels inhibitors, such as tetrodotoxin (TTX) and ω-conotoxin (CTX), respectively. Then the antagonist of inositol trisphosphate receptor, TMB-8, totally abolishes the effect of NMDA on AA incorporation into PI. The lowering of AA incorporation evoked by NMDA is significantly diminished by nitric oxide (NO) synthase inhibitor,N G-nitro-l-arginine (NNLA). Further studies were carried out with NO donor(s) to explain the mechanism of NO action in the inhibition of AA incorporation into PI. Our results suggest the following sequence of events: opening of voltage-dependent sodium and calcium channels, subsequent activation of PI-4,5-bisphosphate-specific phospholipase C (PLC), elevation of inositol trisphosphate (IP3)-sensitive calcium ions, stimulation of NO production and NO-mediated S-nitrosylation, or free radical effect on enzymes involved in AA incorporation. Our data suggest that NO-mediated events may be responsible for NMDA-evoked inhibition of AA incorporation into PI of synaptoneurosomal membrane.

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Abbreviations

VSSC:

voltage-sensitive sodium channel

VSCC:

voltage-sensitive calcium channel

NMDA:

N-methyl-d-aspartate receptor

IP3 :

inositol trisphosphate

PLC:

phosphatidylinositol-4,5-bis-phosphate-specific phospholipase C

AA-CoA-S:

arachidonyl-CoA synthase

AA-CoA-T:

arachidonyl-CoA lysophospholipid acyltransferase

NOS:

nitric oxide synthase

NO:

nitric oxide

TTX:

tetrodotoxin

CTX:

ω-conotoxin, APV-2, amino-5-phosphovaleric acid

TMB-8:

8-(Diethylamino)octyl 3,4,5-trimethoxybenzoate

NNLA:

N G-nitro-l-arginine

SNP:

sodium nitroprusside

ASC:

ascorbate

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Authors and Affiliations

  1. Department of Cellular Signalling, Medical Research Center, Polish Academy of Sciences, 3 Dworkowa St., PL-00784, Warsaw, Poland

    Marek Samochocki, Malgorzata Chalimoniuk & Joanna Strosznajder

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  1. Marek Samochocki
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  2. Malgorzata Chalimoniuk
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  3. Joanna Strosznajder
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Samochocki, M., Chalimoniuk, M. & Strosznajder, J. Nitric oxide responsible for NMDA receptor-evoked inhibition of arachidonic acid incorporation into lipids of brain membrane. Molecular and Chemical Neuropathology 29, 79–92 (1996). https://doi.org/10.1007/BF02815195

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  • DOI: https://doi.org/10.1007/BF02815195

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