Effect of cAMP-elevating drugs on Ca2+ efflux and actin polymerization in peritoneal macrophages stimulated with...

To investigate intracellular cAMP inhibitory mechanisms related to migration of guinea-pig peritoneal macrophages, we examined the effects of cAMP-elevating drugs on the Ca2+ efflux and actin polymerization in macrophages stimulated with fMet-Leu-Phe, a chemotactic peptide. The stimulation with 1 X 10(-8) M fMet-Leu-Phe enhanced the Ca2+ efflux, and induced actin polymerization. Dibutyryl cAMP, theophylline and papaverine, which continuously increased the levels of intracellular cAMP, inhibited the enhancement of Ca2+ efflux and induction of actin polymerization by fMet-Leu-Phe. On the other hand, isoproterenol, which transiently increased the cAMP level, inhibited only the early phase of Ca2+ efflux and not the actin polymerization. As additions of both cAMP and cAMP-dependent protein kinase did not modify the Ca2+ uptake of phagocytic vesicles, the inhibition of Ca2+ efflux by these drugs may be due to the inhibition of the Ca2+ release from the intracellular store site(s). The cAMP-elevating drugs increased the monomeric actin content without change in the total actin content, indicating an induction of the depolymerization of filamentous actin. From these findings, we conclude that the inhibition of macrophage migration induced by cAMP may be due to the inhibition of both the increase of intracellular Ca2+ concentration and actin polymerization. Furthermore, the intracellular levels of cAMP probably play a role in regulating actin states in the macrophages.