Phorbol esters induce nitric oxide synthase and increase arginine influx in cultured peritoneal macrophages

Abstract
Incubation of peritoneal macrophages with β‐phorbol 12,13‐dibutyrate promotes a time‐dependent release of NO to the incubation medium. This effect was antagonized by LPS, a well known inducer of nitric oxide synthase (NOS) expression in macrophages, and was inhibited by N G‐methyl‐l‐arginine and N ω‐nitro‐l‐arginine. An increase in intracellular cGMP and NOS activity was observed in parallel with NO release. The induction of NOS was accompanied by a stimulation of arginine influx within the cell. These results suggest that activation of protein kinase C by phorbol esters is sufficient to promote NOS induction in macrophages.