INHIBITION OF HISTAMINE SYNTHESIS BY GLYCYRRHETINIC ACID IN MAST-CELLS COCULTURED WITH SWISS 3T3 FIBROBLASTS

The effect of glycyrrhetinic acid (18-O-beta-glycyrrhetinic acid, GA) on histamine metabolism was investigated in cultured mast cells (CMCs) cocultured with Swiss 3T3 fibroblasts. GA strongly inhibited histamin e synthesis in the cocultured CMCs. Since 50 mu M GA inhibited about 8 0% of histidine decarboxylase (HDC) activity, the inhibitory activity of GA for histamine synthesis was considered to be derived from the in hibition of HDC activity. The number of berberine-sulfate-positive cel ls also decreased in the presence of GA, which indicated that maturati on of CMCs was inhibited by GA. Furthermore, we examined the effect of GA on the mRNA expression of novel protein kinase C delta (nPKC delta ), a major isoform of CMCs, by Northern blot analysis. The expression of nPKC delta mRNA in the presence of GA was significantly lower than in the absence of GA. These results suggest the possibility that the i nhibition of histamine synthesis by GA is regulated by nPKC delta.