Yamada N, Kadowaki S, Takahashi K, Umezu K
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
Biochem Pharmacol. 1992 Sep 25;44(6):1211-3. doi: 10.1016/0006-2952(92)90387-x.
Repirinast (MY-5116; isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylate) is an anti-allergic drug of demonstrated effectiveness for treating bronchial asthma in humans. MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid), the major active metabolite of repirinast, inhibits antigen-induced histamine release from sensitized rat peritoneal exudate cells (PEC). When purified rat mast cells were treated with MY-1250 (2.5 x 10(-5) M) for 1 min, phosphorylation of a specific mast cell protein of apparent molecular mass of 78 kDa was observed as previously reported for sodium cromoglycate (SCG). Phosphorylation of this protein induced by MY-1250 and SCG occurred in a concentration-dependent manner with IC50 values of 2.0 x 10(-7) and 1.4 x 10(-5) M, respectively. MY-1250 did not inhibit calcium ionophore A23187 (1 microgram/mL)-induced histamine release from rat PEC. In the presence of calcium ionophore A23187 (1 microgram/mL), phosphorylation of this protein induced by MY-1250 was not evident. In conclusion, MY-1250 induced phosphorylation of a 78-kDa protein in rat mast cells and MY-1250 may inhibit histamine release by regulating phosphorylation of this protein in rat mast cells.
瑞吡司特（MY-5116；5,6-二氢-7,8-二甲基-4,5-二氧代-4H-吡喃并[3,2-c]喹啉-2-羧酸异戊酯）是一种已证明对治疗人类支气管哮喘有效的抗过敏药物。瑞吡司特的主要活性代谢产物MY-1250（5,6-二氢-7,8-二甲基-4,5-二氧代-4H-吡喃并[3,2-c]喹啉-2-羧酸）可抑制抗原诱导的致敏大鼠腹腔渗出细胞（PEC）释放组胺。当用MY-1250（2.5×10⁻⁵M）处理纯化的大鼠肥大细胞1分钟时，观察到一种表观分子量为78 kDa的特定肥大细胞蛋白发生磷酸化，这与先前报道的色甘酸钠（SCG）的情况相同。MY-1250和SCG诱导的这种蛋白磷酸化呈浓度依赖性，IC50值分别为2.0×10⁻⁷和1.4×10⁻⁵M。MY-1250不抑制钙离子载体A23187（1微克/毫升）诱导的大鼠PEC释放组胺。在存在钙离子载体A23187（1微克/毫升）的情况下，MY-1250诱导的这种蛋白磷酸化不明显。总之，MY-1250诱导大鼠肥大细胞中78 kDa蛋白磷酸化，且MY-1250可能通过调节大鼠肥大细胞中该蛋白的磷酸化来抑制组胺释放。
