EXTRACELLULAR ATP POTENTIATES NITRIC-OXIDE SYNTHASE EXPRESSION INDUCED BY LIPOPOLYSACCHARIDE IN RAW-264.7 MURINE MACROPHAGES

Inducible nitric oxide synthase (iNOS) activity in the murine macropha ge cell line RAW 264.7 was increased from two- to four-fold after co-e xposure of the cells to low doses of bacterial lipopolysaccharide (LPS ) and micromolar ATP, compared to LPS alone. Extracellular ATP and its analogs ''per se'', i.e. without LPS, were not able to induce iNOS ac tivity. The stimulating effect of UTP too, the concentration range of activity (1-100 mM nucleotides) and the rank of potency (ATP-gamma-S = AMP-PNP > ATP = ADP > > AMP-CPP = UTP) seem to indicate an involvemen t of P-2y-type purinergic receptors. GTP, CTP and adenosine were virtu ally ineffective. These data suggest that binding of extracellular nuc leotides to purinergic receptors may increase nitric oxide production by macrophages. This effect might occur in pathological conditions (i. e. inflammation/infection or trauma) where significant amounts of intr acellular ATP can be released due to cellular damage. (C) 1994 Academi c Press, Inc.