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The 4-acyl-isocoumarins which inhibit compound 48/80-induced histamine release were studied to determine whether or not they could inhibit IgE-mediated and mannan-induced histamine release from isolated rat peritoneal mast cells. The IgE-mediated release was induced mainly in the isolated rat peritoneal cells sensitized in vitro with mouse IgE, and released histamine was assayed by fluorometry. Oosponol (4-hydroxyacetyl-8-hydroxyisocoumarin) and 8-deoxy-oosponol glycinate showed inhibition of both the IgE-mediated and the mannan-induced histamine release, in the same dose range (2-8 μM and 4-16 μM, respectively). KIT-302 (4-(4'-carboxy-benzoyl)-isocoumarin) and its analogues showed potentiation (to approx. 2-fold) of both the IgE-mediated and the mannan-induced release at lower doses (2-30 μM for KIT-302) and inhibition at higher doses. KIT-302 at the lower doses showed potentiation of ATP-induced histamine release and also of the second stage of the IgE-mediated release. Inhibitory effect of KIT-302 on the 48/80-induced histamine release was also observed in Ca++-free medium.

Effect of 4-acyl-isocoumarins on IgE-mediated and mannan-induced histamine release from isolated rat mast cells.