Stimulated release of arachidonic acid by agonists of the peroxisome proliferator-activated receptor and retinoic acid receptors.
Release of arachidonic acid from rat liver cells is stimulated after a 6-hour incubation with 9-cis retinoic acid, all trans retinoic acid, the selective peroxisome proliferator-activated receptor-gamma synthetic thiazolidinedione, ciglitazone, the cyclopentenones, 15-deoxy-Delta(12,14) PGJ2 and PGA1 and the non-steroidal anti-inflammatory drugs, celecoxib and indomethacin. The rates of the release stimulated by 15-deoxy-Delta(12,14) PGJ2 differ from those observed with celecoxib. Arachidonic acid release by9-cis retinoic acid in the presence of either ciglitazone or trans retinoic acid is synergistic. It is additive in the presence of celecoxib. Cycloheximide and actinomycin inhibit the release of arachidonic acid stimulated by 15-deoxy-Delta(12,14) PGJ2 but not by celecoxib. The findings indicate that agonists of the peroxisome proliferator-activated receptor-gamma and retinoic acid receptors stimulate the release of arachidonic acid. The mechanisms involved may differ in the cases of 15-deoxy-Delta(12,14) PGJ2 and celecoxib.
Levine
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Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA. llevine@brandeis.edu
D000077556:Alitretinoin; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D000068579:Celecoxib; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology; D011720:Pyrazoles; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists*; D014212:Tretinoin / Q000494:pharmacology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011454:Prostaglandins A; D011720:Pyrazoles; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D013449:Sulfonamides; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D003609:Dactinomycin; D000077556:Alitretinoin; D016718:Arachidonic Acid; D014212:Tretinoin; D003513:Cycloheximide; C089946:2,4-thiazolidinedione; D000068579:Celecoxib; D015230:Prostaglandin D2; C039671:ciglitazone; C100573:prostaglandin A1; D007213:Indomethacin