[The effect of phosphatidylinositol kinase inhibitors on store-dependent Ca2(+)-transport in macrophages].

Using Fura-2AM microfluorimetry the role of phosphatidylinositol kinases in the regulation of Ca2+ signals induced by purinergic agonist ATP and endoplasmic Ca2(+)-ATPase inhibitor thapsigargin in rat peritoneal macrophages was investigated. It was shown that two structurally distinct phosphatidylinositol 3- and phosphatidylinositol-4-kinases inhibitors wortmannin and LY294002 showed a dose- dependent effect on store-dependent Ca2(+)-entry, induced by thapsigargin or ATP. The data suggest that phosphatidylinositol 3- and phosphatidylinositol-4-kinases play an important role in the activation of store-dependent Ca2(+)-entry in macrophages and that their effect might be mediated by their influence on actin cytoskeleton. The results are compatible with the "secretion-like coupling model" for store-dependent Ca2(+)-entry in macrophages based on a reversible trafficking and coupling of the Ca2+ store with the plasma membrane which suggests the involvement of microfilaments and phosphatidylinositol kinases.