EXTRACELLULAR ATP ENHANCES MESSENGER-RNA LEVELS OF NITRIC-OXIDE SYNTHASE AND TNF-ALPHA IN LIPOPOLYSACCHARIDE-TREATED RAW-264.7 MURINE MACROPHAGES

Extracellular ATP potentiates, by activation of P2y-type purinergic re ceptors, the production of NO induced by low doses of lipopolysacchari de (LPS) in the murine macrophagic cell line RAW 264.7 (Tonetti et al. (1994) Biochem. Biophys. Res. Commun. 203, 430-434). Release of TNF-c l, known to be an autocrine factor for iNOS expression, was enhanced, too, following exposure of either LPS-induced or uninduced cells to ex ternally added micromolar ATP. Reverse transcription-PCR experiments s howed that extracellular ATP increases mRNA levels of both inducible N O synthase (iNOS) and of TNF-a to extents comparable to those of enzym atic and biological activities, respectively. These data demonstrate t hat activation of purinergic receptors by extracellular ATP results in an enhanced expression of the iNOS and TNF-alpha genes. (C) 1995 Acad emic Press, Inc.