Carlin G, Djursäter R, Smedegård G
Department of Pharmacology, Kabi Pharmacia Therapeutics, Uppsala, Sweden.
Ann Rheum Dis. 1992 Nov;51(11):1230-6. doi: 10.1136/ard.51.11.1230.
The effects of sulphasalazine on the production of second messenger compounds in human granulocytes have been characterised by various stimuli. The increases in cytosolic calcium, inositol trisphosphate, diacylglycerol, and phosphatidic acid (all important mediators of intracellular signal transduction) triggered by stimulation were inhibited by sulphasalazine. The metabolites 5-amino-salicylic acid and sulphapyridine were less potent inhibitors than the mother compound. It is concluded that sulphasalazine inhibits the synthesis of phosphoinositide derived second messenger compounds at the level of phospholipase C or its regulatory guanosine 5'-triphosphate (GTP) binding protein. Inhibition of phosphatidic acid synthesis was either due to the same mechanism, or to interaction with a phospholipase D regulating GTP binding protein.
柳氮磺胺吡啶对人粒细胞中第二信使化合物产生的影响已通过各种刺激进行了表征。刺激引发的细胞溶质钙、肌醇三磷酸、二酰基甘油和磷脂酸（均为细胞内信号转导的重要介质）的增加受到柳氮磺胺吡啶的抑制。代谢产物5-氨基水杨酸和磺胺吡啶作为抑制剂的效力低于母体化合物。得出的结论是，柳氮磺胺吡啶在磷脂酶C或其调节性鸟苷5'-三磷酸（GTP）结合蛋白水平上抑制磷酸肌醇衍生的第二信使化合物的合成。磷脂酸合成的抑制要么是由于相同机制，要么是由于与调节GTP结合蛋白的磷脂酶D相互作用。
