Stimulation of cyclic 3':5'-guanosine monophosphate levels in rat spleen cells by lipopolysaccharide preparations.
LPS greatly increases cGMP in rat fetal liver cells without affecting cAMP. The present experiments were undertaken to determine whether this effect occurs in an adult tissue, which might be exposed to LPS in vivo. Therefore cyclic nucleotides were measured in adult male rat spleen cells incubated in vitro in the presence or absence of LPS. A clear cGMP elevation was found in cultures treated with LPS. This was first evident at 2 hr and persisted for 4 hr. In contrast, cAMP was unaffected by LPS even in the presence of the phosphodiesterase inhibitor, MIX. CGMP rose progressively with LPS doses ranging from 0.8 to 20 ng, and addition of MIX potentiated the cGMP stimulatory effect. Several LPS concentrates prepared by different techniques and LPS exposed to vigorous heat treatment exhibited cGMP activity, whereas absorption of LPS with Limulus lysate abolished the cGMP response. Thus LPS increases cGMP in rat spleen cells in a dose-and time-dependent manner without affecting cAMP. Although the significance of this cGMP increase is unknown, its occurrence in spleen cells (a tissue likely to come in contact with LPS in vivo), its production by very small quantities of LPS, and the delayed but persistent nature of the effect (analogous to the aciton of cholera toxin on cAMP) are all consistent with an important role for cGMP in the action of LPS on cells.
D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis*; D004926:Escherichia coli / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D012485:Salmonella typhi / Q000378:metabolism; D013154:Spleen / Q000032:analysis / Q000166:cytology* / Q000187:drug effects*; D013268:Stimulation, Chemical
D008070:Lipopolysaccharides; D000242:Cyclic AMP; D006152:Cyclic GMP