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

Primary mixed glial cell cultures treated with lipopolysaccharide (LPS; 1.0 μg/ml) showed biphasic increases of inducible nitric oxide synthase (iNOS) 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 μM), a protein kinase G (PKG) inhibitor, inhibited the LPS-induced iNOS 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 second phase of the LPS-induced glial iNOS expression and its upregulation, which are apparent in the presence of microglial cells. Copyright (C) 1999 Elsevier Science Ireland Ltd.