cAMP analogues and cholera toxin stimulate the accumulation of nitrite in rat peritoneal macrophage cultures

Rat peritoneal macrophages incubated with the two stable analogues of cAMP, dibutyryl-cAMP and 8-bromo-cAMP, as well as with cholera toxin, released nitrite in a dose-dependent manner. Cholera toxin and dibutyryl-cAMP enhanced nitrite release induced by bacterial lipopolysaccharide. The stimulatory effects of all these substances were inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine, dexamethasone and the protein synthesis inhibitor, cycloheximide. Our data indicate that the activation of cAMP-dependent pathway(s) can induce nitric oxide synthesis in rat peritoneal macrophages even in the absence of immunological stimuli, such as exogenous cytokines or lipopolysaccharide, although the exact mechanism of this phenomenon remains to be established.