An antiallergic drug, pemirolast potassium, inhibits inositol 1,4,5-trisphosphate production and Ca2+ mobilization in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells.
An antiallergic drug, pemirolast potassium (TBX) at concentrations between 0.01 and 10 micrograms/ml inhibited antigen (Ag)-stimulated degranulation in RBL-2H3 cells, which have the properties of mucosal mast cells. At the same concentrations, the drug suppressed both the formation of inositol 1,4,5-trisphosphate and the mobilization of Ca2+, indicating the prevention of phospholipase C activation. The production of 1,2-diacylglycerol and phosphatidic acid, which was mainly due to phosphatidylcholine hydrolysis, was also suppressed. Moreover, TBX reduced Ag-induced liberation of arachidonic acid, a precursor of eicosanoids, implying the inhibition of phospholipase A2. These data suggest that TBX inhibits the activation of phospholipase C, leading to decreased formation of the signal transducing molecules necessary for cell activation.
Fujimiya
H
H
Department of Otolaryngology, Gifu University School of Medicine.
Nakashima
S
S
Kumada
T
T
Nakamura
Y
Y
Miyata
H
H
Nozawa
Y
Y
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002118:Calcium / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D015471:Leukemia, Basophilic, Acute / Q000276:immunology* / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D006633:Histamine Antagonists; D011725:Pyridines; D011744:Pyrimidinones; C055139:pemirolast; D015544:Inositol 1,4,5-Trisphosphate; D010740:Phospholipases; D002118:Calcium