Protein kinases regulate the phosphorylation of the GluR1 subunit of AMPA receptors of spinal cord in rats following noxious stimulation.
The present project was designed to investigate the role of protein kinase A (PKA) and protein kinase C (PKC) in the regulation of phosphorylation of the GluR1 subunits of AMPA receptors in the spinal cord of rats after capsaicin injection. We found that after capsaicin injection, a significant upregulation of phosphorylated GluR1 both at Ser(831) and Ser(845) was detected on the side ipsilateral to the injection. Intrathecal treatment with a PKA inhibitor, H89 ([N-[2-((3-bromophenyl)-2-propenyl)amino)ethyl]-5-isoquinoline sulfonamide, HCl), or a PKC inhibitor, NPC15473 (2,6-diamino-N-([1-oxotridecyl)-2-piperidinyl]methyl)hexanamide), significantly blocked the increased phosphorylation at different serine sites without affecting the GluR1 protein itself. Our results suggest that increased phosphorylation of the GluR1 subunit of AMPA receptors contributes to central sensitization following acute peripheral inflammation, and the effect may occur at different phosphorylation sites through the activation of the PKA or PKC protein kinase cascades.
Fang
Li
L
Division of Neurosurgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Wu
Jing
J
Lin
Qing
Q
Willis
William D
WD
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology*; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D002211:Capsaicin; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D018091:Receptors, AMPA; D012694:Serine