Phorbol esters induce nitric oxide synthase and increase arginine influx in cultured peritoneal macrophages.
Incubation of peritoneal macrophages with beta-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 NG-methyl-L-arginine and N omega-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.
Hortelano
S
S
Instituto de Bioquímica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Genaro
A M
AM
Boscá
L
L
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010529:Peritoneal Cavity / Q000166:cytology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D015240:Phorbol 12,13-Dibutyrate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D011493:Protein Kinase C; D006152:Cyclic GMP