Characterization of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells induced by antigen, compound 48/80 and A 23187

Abstract

We studied thein vitro effects of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells. These cells exposed to ascaris antigen, compound 48/80 or the ionophore A 23187 concentration-dependently released histamine. About a 30–40% histamine release was obtained by 1×10⁻⁴ g/ml of antigen, 1×10⁻⁷ g/ml of compound 48/80 and A 23187. FPL-52694 (10⁻⁹–10⁻⁴ g/ml) concentration-dependently inhibited the histamine release from mast cells in response to antigen (1×10⁻⁴ g/ml) and compound 48/80 (1×10⁻⁷ g/ml), but only slightly inhibited the histamine release induced by A 23187 (1×10⁻⁷ g/ml). Similar results were obtained with disodium cromoglycate (DSCG), in the same dose ranges. However, the inhibitory activity of FPL-52694 on histamine release by antigen and compound 48/80 was approximately 10 times more potent than that of DSCG at certain coincentrations. Tachyphylaxis was observed when these two agents were preincubated with mast cells for 10 min. These results show FPL-52694 to be a novel mast cell stabilizer.