MY-1250, a major metabolite of the anti-allergic drug repirinast, induces phosphorylation of a 78-kDa protein in rat mast cells

Abstract Repirinast (MY-5116; isoarnyl 5,6-dihydro-7,8-diniethyl-4,5-dioxo-4 H -pyrano[3,2- c ]quino-line-2-carboxylate) is an anti-allergic drug of demonstrated effectiveness for treating bronchial asthma inhumans. MY-1250 (5,6-dihydro-7,8-dimethyl-4,5-dioxo-4 H -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 × 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 ic 50 values of 2.0 × 10 −7 and 1.4 × 10 −5 M, respectively. MY-1250 did not inhibit calcium ionophore A23187 (1 μg/mL)-induced histamine release from rat PEC. In the presence of calcium ionophore A23187 (1 μg/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.