MY-1250, a major metabolite of the anti-allergic 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 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.
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
N
N
Yamada
S
S
Kadowaki
K
K
Takahashi
K
K
Umezu
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004347:Drug Interactions; D006633:Histamine Antagonists / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D015363:Quinolones / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D011506:Proteins; D015363:Quinolones; D000001:Calcimycin; C048522:repirinast; C049488:MY 1250