CAMP ANALOGS AND CHOLERA-TOXIN STIMULATE THE ACCUMULATION OF NITRITE IN RAT PERITONEAL MACROPHAGE CULTURES

Rat peritoneal macrophages incubated with the two stable analogues of cAMP, dibutyrylo-cAMP and 8-bromo-cAMP, as well as with cholera toxin, released nitrite in a dose-dependent manner. Cholera toxin and dibuty rylo-cAMP enhanced nitrite release induced by bacterial lipopolysaccha ride. The stimulatory effects of all these substances were inhibited b y the nitric oxide synthase inhibitor N-G-monomethyl-L-arginine, dexam ethasone and the protein synthesis inhibitor, cycloheximide. Our data indicate that the activation of cAMP-dependent pathway(s) can induce n itric oxide synthesis in rat peritoneal macrophages even in the absenc e of immunological stimuli, such as exogenous cytokines or lipopolysac charide, although the exact mechanism of this phenomenon remains to be established.