Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms

Détails

ID Serval
serval:BIB_75022EC0ECB4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms
Périodique
Molecular Pharmacology
Auteur(s)
Volterra  A., Trotti  D., Racagni  G.
ISSN
0026-895X (Print)
Statut éditorial
Publié
Date de publication
11/1994
Volume
46
Numéro
5
Pages
986-92
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
Reuptake of glutamate in astrocytes, a critical mechanism involved in the maintenance of physiological excitatory amino acid neurotransmission, is inhibited by both arachidonic acid (AA) and reactive oxygen species (ROS), via incompletely defined molecular mechanisms. Because ROS are generated during AA metabolism and AA can be released as a result of ROS-mediated phospholipase A2 activation, it seems likely that their effects on uptake are mediated by a common mechanism. However, here we show that rapid (10-min) uptake inhibitions by AA or by ROS generated by the xanthine plus xanthine oxidase (XO) reaction are selectively abolished by distinct agents; bovine serum albumin (BSA) acts only on AA, whereas the scavenger enzymes superoxide dismutase (SOD) and catalase (CAT) and the disulfide-reducing agent dithiothreitol (DTT) act only on ROS. Moreover, when added together, xanthine/XO and AA decrease uptake in a fully additive manner. In particular, the effect of xanthine/XO is seen also in the presence of maximal AA inhibition. No major signs of cell damage or chemical reaction between AA and radicals accompany their cumulative effects on uptake. Finally, uptake inhibition elicited by AA and xanthine/XO together is attenuated but not blocked by either BSA, DTT, or SOD/CAT individually, whereas it is fully blocked and substantially reversed by a combination of SOD/CAT and BSA or SOD/CAT, DTT, and BSA. Together, these data indicate that AA and ROS act on glial glutamate transport via distinct noninteracting mechanisms. Therefore, they could independently and additively contribute to the impairment of reuptake function, a phenomenon observed in pathological conditions such as ischemia/reperfusion injury.
Mots-clé
Animals Arachidonic Acid/antagonists & inhibitors/*physiology Astrocytes/metabolism Biological Transport/drug effects/physiology Glutamic Acid/*metabolism Rats *Reactive Oxygen Species Sodium/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 15:37
Dernière modification de la notice
03/03/2018 18:22
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