Inhibitory mechanism of tritoqualine on histamine release from mast cells.
Tritoqualine (TRQ, (+)-(R*)-7-amino-4,5,6-triethoxy-3-[(R*)-5,6,7, 8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin++ +-5-yl] phthalide) strongly inhibited the increased metabolism of [3H]arachidonic acid-labeled phospholipid and 45Ca2+ influx in mast cells stimulated by compound 48/80 (compd 48/80), Concanavalin A (Con A) plus phosphatidylserine (PS), or 2,4-dinitrophenyl-coupled-ascaris extracts (DNP-asc). However, TRQ did not disturb the binding of 14C-labeled compd 48/80 to the mast cell membrane. The activity of calmodulin purified from mastocytoma P-815 cells was inhibited by TRQ at IC50 1.0 microM. From these results, it is concluded that the inhibitory mechanism of TRQ on stimulus-induced histamine release from mast cells may be mediated at least partially by the inhibition of Ca2+ influx and calmodulin activity.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010718:Phosphatidylserines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D001095:Arachidonic Acids; D002147:Calmodulin; D007546:Isoquinolines; D010718:Phosphatidylserines; D003208:Concanavalin A; D016718:Arachidonic Acid; D003189:p-Methoxy-N-methylphenethylamine; C003722:tritoqualine; D002118:Calcium