CALCIUM ANTAGONIST-LIKE ACTIONS OF COUMARINS ISOLATED FROM "QIAN-HU" ON ANAPHYLACTIC MEDIATOR RELEASE FROM MAST CELL INDUCED BY CONCANAVALIN A

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The effects of coumarins on anaphylactic mediator release from rat mast cells were investigated. Since Pd-Ia (3'-angeloyloxy-4'-acetoxy-3', 4'-dihydroseselin) causes relaxation of smooth muscle unhibiting calcium influx, and since mediator release is a calcium-dependent process, studies were made on whether coumarins block calcium influx into rat mast cells stimulated by concanavalin A. Pd-Ia isolated from Peucedanum praeruptorum DUNN and related compounds, named Pd-C-II, Pd-C-III and Pd-C-IV, from Peucedanum decursivum MAXIM., (Angelica decursiva FR. et SAV.) inhibited mediator release from purified mast cells induced by concanavalin A with phosphatidylserine; their IC_<50> values were 79,100,102 and 73 μM, respectively. Pd-III, decursidin and water-soluble analogues of Pd-Ia (Pd-Ia-OH, Pd-Ia-OCH_2CH_3) did not inhibit the release. Thus the inhibitory actions of coumarins on calcium influx seemed to depend on the chemical structures of these compounds ; an acetoxyl residue at position 3' or 4' on the seselin or xanthyletin skeleton might be essential for an inhibitory. Furthermore, Pd-Ia and Pc-C-III caused more than 40% reduction in ^<45>Ca uptake induced by concanavalin A, whereas decursidin had little effect on it. Therefore, the inhibitions of mediator release of mast cells by some of coumarins from "Qian-Hu" seem to depend on their effect in blocking calcium influx.
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