Immunopharmacological studies on TBX, a new antiallergic drug. (2) inhibitory effects on histamine release from peritoneal mast cells and lung fragments of rats.
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概要
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The ability of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a]pyrimidin-4-one potassium salt (TBX) to inhibit histamine release from both peritoneal exudate cells (PEC) containing mast cells and lung fragments of rats was investigated in vitro. Low concentrations of TBX dose-dependently inhibited IgE-mediated histamine release from PEC of passively sensitized animals; its IC50 was 5.1×10<SUP>-9</SUP> g/ml. When TBX was added simultaneously with the antigen challenge, the highest inhibition was obtained. In contrast, extension of preincubation time with the agent resulted in a marked decrease in the inhibition of histamine release. The potent inhibition of histamine release by TBX was observed equally in glucose-free as well as complete Tyrode's solution, whereas TBX reduced its inhibitory action in Ca<SUP>2+</SUP>-free or D<SUB>2</SUB>O -supplemented medium. In addition, TBX inhibited compound 48/80- but not calcium ionophore A23187-induced histamine release from normal PEC. With regard to the intracellular cyclic AMP level in normal PEC, it was significantly enhanced by a high concentration of TBX (10<SUP>-3</SUP> g/ml). TBX also inhibited antigen-induced histamine release from lung fragments of actively immunized animals. Interestingly, TBX displayed non-competitive inhibition of cyclic AMP-dependent phosphodiesterase derived from lung homogenates; its K<SUB>1</SUB> value was 8.70×10<SUP>-4</SUP> M.
- 公益社団法人 日本薬理学会の論文
著者
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Yanagihara Yukiyoshi
Clinical Research Center For Allergy And Rheumatology National Hospital Organization Sagamihara Nati
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Shida Takao
Clinical Research Center For Rheumato-allergology National Sagamihara Hospital
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KASAI Hiroshi
Research Laboratories, Tokyo Tanabe Pharmaceutical Co., Ltd.
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SHIDA Takao
Clinical Research Center for Allergy, National Sagamihara Hospital
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