Calcium antagonist-like actions of coumarins isolated from "Qian-Hu" on anaphylactic mediator release from mast cell induced by concanavalin A.
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 by inhibiting 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 anaphylactic mediator release from purified mast cells induced by concanavalin A with phosphatidylserine; their IC50 values were 79, 100, 102 and 73 microM, respectively. Pd-III, decursidin and water-soluble analogues of Pd-Ia (Pd-Ia-OH, Pd-Ia-OCH2CH3) 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 effect. Furthermore, Pd-Ia and Pd-C-III caused more than 40% reduction in 45Ca 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 effects in blocking calcium influx.
Suzuki
T
T
Kobayashi
Y
Y
Uchida
M K
MK
Sakakibara
I
I
Okuyama
T
T
Shibata
S
S
D000707:Anaphylaxis / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002681:China; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D037121:Plant Lectins; D010946:Plants, Medicinal / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D003374:Coumarins; D037121:Plant Lectins; D003208:Concanavalin A; D002118:Calcium