Inhibition of histamine release and phosphatidylcholine metabolism by 5'-deoxy-5'-isobutylthio-3-deazaadenosine.
3-deaza-SIBA, a postulated analogue of S-adenosylhomocysteine, inhibited the IgE-mediated histamine release and blocked both the choline uptake by the rat basophilic leukemia cells and the incorporation of choline into phosphatidylcholine and lysophosphatidylcholine. Unlike inhibitors of methylation which inhibit only dextran- and IgE-mediated reactions, 3-deaza-SIBA also blocked the histamine release from mast cells induced by other secretagogues, such as compound 48/80, ionophore A23187, polymyxin B and ATP. 3-Deaza-SIBA may perturb membrane functions of basophilic leukemia cells and mast cells by inhibiting the biosynthesis of phosphatidylcholine via choline incorporation, the turnover of which is probably required for cellular degranulation and the release of histamine. Previous studies with 3-deaza-SIBA have been mainly interpreted in terms of its structural similarity to S-adenosylhomocysteine and its potential use as an inhibitor of methylation reactions. In light of our present findings, experiments utilizing 3-deaza-SIBA as a biochemical probe have to be carefully interpreted.
D000818:Animals; D001491:Basophils / Q000378:metabolism; D002478:Cells, Cultured; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology*; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology*
D010713:Phosphatidylcholines; D012263:Ribonucleosides; C017194:5'-deoxy-5'-(isobutylthio)-3-deazaadenosine; D014372:Tubercidin