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 microg/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 microM), 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.
Choi
S H
SH
Department of Pharmacology, Korea University College of Medicine, Seoul, South Korea.
Shin
K H
KH
Kang
S W
SW
Chun
Y S
YS
Chun
B G
BG
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C073601:KT 5823; D003995:Dibutyryl Cyclic GMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP