Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E(2) concentration in rat brain.
Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A(2)(cPLA(2)). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E(2) (PGE(2)), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca(2+)-independent iPLA(2) (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA(2) and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.
Bosetti
Frances
F
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg 10 Rm. 6N202, Bethesda, MD 20892, USA. frances@mail.nih.gov
Rintala
J
J
Seemann
R
R
Rosenberger
T A
TA
Contreras
M A
MA
Rapoport
S I
SI
Chang
M C
MC
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D054522:Group VI Phospholipases A2; D007527:Isoenzymes / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D018692:Antimanic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D018021:Lithium Chloride; D015232:Dinoprostone