Inhibition of leukotriene C and leukotriene D biosynthesis.

Abstract

Leukotriene C4 and leukotriene D4 are slow reacting substances produced by mouse mastocytoma cells and rat basophilic leukemia cells, respectively. Serine x borate complex, an inhibitor of glutamyl transpeptidase (EC 2.3.2.2), prevented the formation of the biologically more potent leukotriene D4 and caused accumulation of leukotriene C4 in rat basophilic leukemia cell suspensions. 5,8,11-Eicosatriynoic acid, a lipoxygenase inhibitor, prevented the biosynthesis of leukotriene C4 (ID50, 5 microM) by mastocytoma cells. The results demonstrate that gamma-glutamyl transpeptidase is involved in the biosynthesis of leukotriene D4 and suggest that leukotriene C4 is formed as an intermediate.