Studies on the effects of disease-modifying antirheumatic drugs on lipoxygenase product synthesis in human neutrophils in vitro.
The disease-modifying antirheumatic drugs sodium aurothiomalate, D-penicillamine and chloroquine phosphate were tested on leukotriene (LT) synthesis in human blood polymorphonuclear leukocytes stimulated with either the ionophore A23187, zymosan or f-Met-Leu-Phe. Lipoxygenase products were analyzed by reversed-phase high-performance liquid chromatography. The study demonstrated that the drugs can either inhibit or enhance 5-lipoxygenase product synthesis in human leukocytes, depending on the stimulus used to activate the cells and the drug concentration. The data also suggested that increased substrate availability accounted for the stimulatory effects of the drugs on leukotriene synthesis.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010396:Penicillamine / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015289:Leukotrienes; D006052:Gold Sodium Thiomalate; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C023676:chloroquine diphosphate; D002738:Chloroquine; D015054:Zymosan; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase; D010396:Penicillamine; D015232:Dinoprostone