Effect of forskolin on prostaglandin synthesis by mouse resident peritoneal macrophages.

The relationship between cyclic 3',5'-adenosine monophosphate (cAMP) and prostaglandin (PG) synthesis was investigated in the mouse resident peritoneal macrophage. Macrophages were established as monolayer cultures in petri dishes. After addition of various agents, culture media and cells were removed for PG and cAMP analysis by standard radiochromatographic techniques and radioimmunoassay respectively. Forskolin, a potent receptor-independent adenylate cyclase activator, rapidly increased cAMP synthesis within 5 min in a dose related fashion in both non-treated macrophages and macrophages treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, forskolin markedly reduced both 6-keto-PGF1 alpha and PGE2 synthesis induced by TPA and this inhibition was inversely correlated with increases with cAMP generation. In contrast, cholera toxin failed to mimic the inhibitory action of forskolin on PG synthesis even though it induced similar increases in cAMP; however this increase was only evident after a lag period of at least 1 h. Additionally, forskolin, but no cholera toxin inhibited PG synthesis and zymosan phagocytosis when these cells were activated with zymosan particles. These observations, therefore, suggest that a rise in cAMP is not always correlated with a reduction in PG synthesis.