Inhibition of compound 48/80-mediated histamine release from isolated rat mast cells by oosponol-related compounds (4-acyl-isocoumarins).
Oosponol (4-hydroxymethylketone-8-hydroxyisocoumarin) is a metabolic product isolated from Oospora astringens which originated from house dust in a room of an asthmatic patient. The compound and the structurally related isocoumarins were studied to determine the inhibition of histamine release induced by compound 48/80 from isolated rat peritoneal mast cells. The released histamine was assayed by fluorometry. The compounds tested were not observed to release histamine. Some of 4-acyl-isocoumarins inhibited the histamine release at doses less than 10 micrometers, whereas the 3-acyl- and the 4-alkyl-compounds were not effective at doses over 100 microns. The pretreatment of mast cell with the compound for 15 min before the application of compound 48/80 was more effective than the simultaneous administration. The mode of inhibitory action of KIT-302, 4-(4'-carboxy-benzoyl)-isocoumarin, was non-competitive antagonism to compound 48/80 on the mast cells.
D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D003374:Coumarins; D003189:p-Methoxy-N-methylphenethylamine