Arachidonic acid metabolism in guinea pig skin: effects of chloroquine.
We investigated the effect of chloroquine (CQ) on the metabolism of exogenous [14C]arachidonic acid by guinea pig skin homogenates. The major cyclooxygenase product formed by the homogenates was PGD2; smaller quantities of PGE2 were formed. CQ suppressed the production of PGD2 and PGE2 in a dose-dependent fashion with an IC50 of 230 microM. This suppression was due to a cyclooxygenase inhibition, since the formation of the prostaglandins from exogenous endoperoxide PGH2 was unaffected. The skin homogenates also exhibited an active lipoxygenase pathway leading to HETE formation. The effect of CQ on the lipoxygenase activity was far less marked than its effect on the cyclooxygenase. CQ is an inhibitor of the cutaneous cyclooxygenase, and this effect may contribute to its anti-inflammatory action in various dermatological disorders.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D002738:Chloroquine / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008084:Lipoxygenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
D001095:Arachidonic Acids; D011463:Prostaglandins H; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002738:Chloroquine; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases