THE EFFECT OF PHOSPHATIDYLINOSITOL KINASE INHIBITORS ON STORE-DEPENDENT Ca2+-ENTRY IN MACROPHAGES
L. S. Kurilova, Z. I. Krutetskaya, O. E. Lebedev
Chair of Biophysics of St. Petersburg State University;
e-mail: cozzy@mail.ru
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.
Key words: peritoneal macrophages, store-dependent Ca2+-entry, phosphatidylinositol
kinases, wortmannin, LY294002
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