5-Lipoxygenase and cyclooxygenase mRNA expression in rat hippocampus:early response to glutamate receptor activation by kainate.
Recent research has identified in central nervous system neurons the expression of two enzymes from the inflammatory pathway of the metabolism of arachidonic acid, the 5-lipoxygenase (5LOX) and the cyclooxygenase-2 (COX2). Expression of both enzymes appears to be upregulated during aging; upregulated 5LOX/COX2 expression in neurons may be responsible for the increased neuronal vulnerability to degeneration. Involvement of the excitatory neurotransmitter glutamate in aging-associated neurodegeneration has also been suggested. Stimulation of glutamate receptors by kainic acid (kainate) has been shown independently to affect the brain expression of 5LOX or COX2. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to measure the contents of mRNAs we found 3h after kainate injection (intraperitoneally; 10 mg/kg) increased mRNA levels of 5LOX and COX2, but not that of COX1 in the hippocampus of rats. Pretreatment with the COX2 inhibitor NS-398 (9 mg/kg, 1h prior to kainate) inhibited the kainate-stimulated increase of 5LOX and COX2 mRNA levels. Our results indicate that hippocampal expression of both 5LOX and COX2 increases rather promptly when glutamate receptors are stimulated by kainate. The mechanism of how NS-398 inhibits this action of kainate should be further investigated.
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The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA. hmanev@psych.uic.edu
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D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D021983:Cyclophilins / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000235:genetics*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D021983:Cyclophilins; D007608:Kainic Acid