Kainic acid rapidly induces cyclooxygenase (COX)-2 in piglet cerebral cortex.
Ischemia/reperfusion (I/R) results in a robust induction of cyclooxygenase (COX)-2 in the newborn brain via unknown mechanisms, but glutamate release and activation of KA receptors may be involved. We examined effects of local KA (3-300 micromol/l for 10 min) treatment on cortical COX-2 expression in anesthetized piglets using a closed cranial window. Treated and corresponding control tissue samples were collected 0.5-10 h after treatment. COX-2 mRNA and protein levels were assessed using RNase protection assay and immunohistochemistry, respectively. KA elicited reproducible dose-dependent increases in cortical COX-2 mRNA unaffected by indomethacin or N(G)-nitro-L-arginine methyl ester pretreatment. COX-2 mRNA levels were elevated at 30 min, peaked at 2 h, but remained enhanced for up to 10 h after KA. Neuronal COX-2 immunoreactivity was also enhanced compared with the control side in all cortical layers 8h after KA. In summary, activation of KA receptors may be involved in the neuronal induction of COX-2 after I/R in the newborn.
Domoki
F
F
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157-1010, USA.
Thrikawala
N
N
Robins
G S
GS
Bari
F
F
Busija
D W
DW
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000201:enzymology*; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects
D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin