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 macrophage cell line RAW 264.7 was increased from two- to four-fold after co-exposure 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 activity. 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 involvement of P2y-type purinergic receptors. GTP, CTP and adenosine were virtually ineffective. These data suggest that binding of extracellular nucleotides 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 intracellular ATP can be released due to cellular damage.