Sulfasalazine inhibits lyso-PAF: acetyl-COA acetyltransferase.
Sulfasalazine produced a dose-dependent inhibition of the enzymatic synthesis of platelet-activating factor (PAF) in lysates of rat pleural neutrophils, with an IC50 of 50 microM. Major metabolites of sulfasalazine, 5-aminosalicylic acid and sulfapyridine, inhibited this enzymatic synthesis at much higher concentrations. Inhibition of arachidonate 5-lipoxygenase by sulfasalazine and its major metabolites was also observed at higher concentrations (2-3 mM). Because PAF is a potent mediator of inflammatory responses, an inhibition of PAF synthesis by sulfasalazine may contribute to its therapeutic actions in conditions such as ulcerative colitis and rheumatic illnesses.
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
L D
LD
Faison
H L
HL
White
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D005122:Exudates and Transudates / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D010994:Pleura / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000494:pharmacology*
D012460:Sulfasalazine; D001094:Arachidonate 5-Lipoxygenase; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase