Guanosine 5 ',3 '-cyclic monophosphate enhances lipopolysaccharide-inducednitric oxide synthase expression in mixed glial cell cultures of rat

Primary mixed glial cell cultures treated with lipopolysaccharide (LPS; 1.0 mu g/ml) showed biphasic increases of inducible nitric oxide synthase (iNO S) mRNA expression 6 h and 24-36 h after LPS treatment. Dibutyryl-guanosine 5',3'-cyclic monophosphate (db-cGMP; 1.0 mM) enhanced the second phase of the LPS-induced iNOS expression 24 and 30 h after LPS stimulation. KT5823 ( 1.0 mu M), a protein kinase G (PKG) inhibitor, inhibited the LPS-induced iN OS expressions at 24 and 30 h and their enhancements caused by db-cGMP. In astrocyte-enriched cultures with reduced microglial contamination, the LPS- induced iNOS expression was decreased, though slightly enhanced by db-cGMP. These results suggest that cGMP/PKG signaling may be involved in the secon d phase of the LPS-induced glial iNOS expression and its upregulation, whic h are apparent in the presence of microglial cells. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.