title: Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E(2) concentration in rat brain.
abstract: 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.
authors.affiliation: 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
authors.forename: Frances
authors.initials: F
authors.lastname: Bosetti
authors.forename: J
authors.initials: J
authors.lastname: Rintala
authors.forename: R
authors.initials: R
authors.lastname: Seemann
authors.forename: T A
authors.initials: TA
authors.lastname: Rosenberger
authors.forename: M A
authors.initials: MA
authors.lastname: Contreras
authors.forename: S I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: M C
authors.initials: MC
authors.lastname: Chang
mesh_terms: 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
chemical_list: 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