MY-1250, A MAJOR METABOLITE OF THE ANTIALLERGIC DRUG REPIRINAST, INDUCES PHOSPHORYLATION OF A 78-KDA PROTEIN IN RAT MAST-CELLS

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 mug/mL)-induced histamine release from rat PEC. In the presence of calcium ionophore A23187 (1 mug/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.