Stimulation by glutamate receptors of arachidonic acid release depends on the Na+/Ca2+ exchanger in neuronal cells.
In primary cultures of striatal neurons, stimulation of N-methyl-D-aspartic acid (NMDA) receptors or associative activation (but not separate activation) of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and metabotropic glutamate receptors (mGluR) strongly increased arachidonic acid (AA) release via activation of phospholipase A2 (PLA2). Depolarizing agents, such as veratridine, were as potent as NMDA in stimulating AA release. However, increasing the intracellular Ca2+ concentration via voltage-sensitive Ca2+ channels did not result in a significant stimulation of PLA2. Substitution of sodium by lithium, a monovalent cation that does not participate in the Na+/Ca2+ exchanger activity but permeates ionotropic glutamate receptor channels, blocked AA release induced by veratridine or AMPA plus mGluR agonists. It also reduced the NMDA-induced AA release, to a lesser extent. The contribution of the Na+/Ca2+ exchanger to the activation of PLA2 after veratridine, NMDA receptor, or AMPA receptor plus mGluR stimulation was confirmed by using a selective inhibitor of the Na+/Ca2+ exchanger.
Dumuis
A
A
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Sebben
M
M
Fagni
L
L
Prézeau
L
L
Manzoni
O
O
Cragoe
E J
EJ
Bockaert
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D014701:Veratridine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D002352:Carrier Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D019831:Sodium-Calcium Exchanger; D010566:Virulence Factors, Bordetella; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007051:Ibotenic Acid; D016718:Arachidonic Acid; D016202:N-Methylaspartate; D014701:Veratridine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D012964:Sodium; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium