Further characterization of the effect of bacterial lipopolysaccharide preparations in cyclic 3',5'-GMP levels: the importance of serum.
Bacterial lipopolysaccharides (LPS) greatly increase cGMP levels in rat fetal liver cells without affecting the concentration of cAMP. This elevation is due to the Lipid A moiety of the LPS molecule, is time and dose dependent, and is markedly potentiated by small amounts of serum. Because of the magnitude of the serum potentiation, a series of experiments was undertaken to further characterize this effect. Although serum was not absolutely necessary for a cGMP response, small amounts increased the cGMP potency of LPS more than 100-fold. Under these same conditions, serum did not greatly affect the ability of nitroprusside to raise cGMP levels or of epinephrine to raise cAMP levels. The effect of serum on the cGMP response was dose dependent and was produced with as little as 1 microliter (0.1% v/v) per culture. Absorption with limulus lysate, heating to 56 degrees C for 30 min, or extensive dialysis did not significantly alter the cGMP enhancing effect of serum. However, albumin and IgG were both inactive at all concentrations tested. Thus, serum produces a large dose dependent enhancement of the LPS induced cGMP response that appears to be selective, i.e. it is not a non-specific protein effect and there is no similar potentiation of nitroprusside stimulated cGMP levels. Furthermore, the cGMP effect of serum is probably not related to substances that opsonize bacteria and is due to a component or components of serum large enough not to be dialyzable.
D000818:Animals; D001798:Blood Proteins; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D007136:Immunoglobulins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012475:Salmonella / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D001798:Blood Proteins; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D012710:Serum Albumin, Bovine; D006152:Cyclic GMP