Nitric oxide responsible for NMDA receptor-evoked inhibition of arachidonic acid incorporation into lipids of brain membrane Authors
Received: 07 July 1995 Revised: 17 October 1995 Accepted: 25 October 1995 DOI:
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, 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 (IP 3)-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 receptor arachidonic acid sodium channel calcium channel nitric oxide cerebral cortex Abbreviations VSSC
voltage-sensitive sodium channel
voltage-sensitive calcium channel
NMDA N-methyl- d-aspartate receptor IP 3
phosphatidylinositol-4,5-bis-phosphate-specific phospholipase C
arachidonyl-CoA lysophospholipid acyltransferase
nitric oxide synthase
ω-conotoxin, APV-2, amino-5-phosphovaleric acid
NNLA N G-nitro- l-arginine SNP
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