Molecular and Chemical Neuropathology

, Volume 29, Issue 1, pp 79–92

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

  • Marek Samochocki
  • Malgorzata Chalimoniuk
  • Joanna Strosznajder
Original Articles

DOI: 10.1007/BF02815195

Cite this article as:
Samochocki, M., Chalimoniuk, M. & Strosznajder, J. Molecular and Chemical Neuropathology (1996) 29: 79. doi:10.1007/BF02815195

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,NG-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.

Index Entries

NMDA receptorarachidonic acidsodium channelcalcium channelnitric oxidecerebral cortex

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

NG-nitro-l-arginine

SNP

sodium nitroprusside

ASC

ascorbate

Copyright information

© Humana Press Inc. 1996

Authors and Affiliations

  • Marek Samochocki
    • 1
  • Malgorzata Chalimoniuk
    • 1
  • Joanna Strosznajder
    • 1
  1. 1.Department of Cellular Signalling, Medical Research CenterPolish Academy of SciencesWarsawPoland