Phosphorylation of AMPA receptor subunits is differentially regulated by phospholipase A2 inhibitors.
Our laboratory recently discovered that the phosphorylation of subunits forming the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of glutamate receptors is regulated by constitutive phospholipase A2 (PLA2) activity in rat brain sections. In the present investigation, arachidonyl trifluoromethyl ketone (AACOCF3) and bromoenol lactone (BEL) were used to compare the influence of calcium-dependent (cPLA2) and calcium-independent (iPLA2) enzymes on phosphorylation of AMPA and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Incubation of rat brain sections with 3 microM BEL enhanced phosphorylation on the serine (Ser) 831 residue of the AMPA receptor GluR1 subunit in synaptosomal P2 fractions, whereas AACOCF3 at the same concentration resulted in increased phosphorylation on residues Ser880/891 of GluR2/3 subunits. These effects were restricted to the AMPA receptor subtype as no changes in phosphorylation were elicited on the NMDA receptor NR1 subunit. The effects of BEL and AACOCF3 were not occluded during blockade of protein phosphatases since AMPA receptor phosphorylation was still apparent in the presence of okadaic acid, indicating that the PLA2 inhibitor-induced increase in AMPA receptor phosphorylation does not rely on a decrease in dephosphorylation reactions. However, pretreatment of rat brain sections with a cell-permeable protein kinase C (PKC) inhibitor prevented BEL- and AACOCF3-induced phosphorylation on the Ser831 and Ser880/891 sites of GluR1 and GluR2/3 subunits, respectively. These results suggest that constitutive cPLA2 and iPLA2 systems may differentially influence AMPA receptor properties and function in the rat brain through mechanisms involving PKC activity.
Ménard
Caroline
C
Département de chimie-biologie, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Que., Canada G9A 5H7. Caroline_Menard@uqtr.ca
Patenaude
Christian
C
Massicotte
Guy
G
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D018091:Receptors, AMPA; C081565:arachidonyltrifluoromethane; D010741:Phospholipases A; D054467:Phospholipases A2