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.
Faison
L D
LD
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
White
H L
HL
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