[Arp2/3 complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages].

The involvement of Arp2/3 complex, which causes actin filament branching, in the effect of drugs glutoxim and molixan was investigated. Using Fura-2AM microfluorimetry it was shown for the first time that Arp2/3 complex inhibitor CK-0944666 almost completely prevents the increase in intracellular Ca2+ concentration, induced by glutoxim or molixan in macrophages. The data suggest the involvement of Arp2/3 complex in the glutoxim and molixan effect on the Ca2+ signalling processes in macrophages.

[The effect of cyclooxygenase and lipoxygenase inhibitors on Ca(2+)-responses induced by glutoxim and molixan in macrophages].

Glutoxim and molixan belong to a new generation of disulfide-containing drugs with immunomodulatory, hepatoprotective and hemopoetic effect. Using Fura-2AM microfluorimetry, the possible involvement of the cyclooxygenase and lipoxygenase pathways of arachidonic acid oxidation in the effect of glutoxim and molixan on the intracellular Ca2+ concentration in rat peritoneal macrophages has been investigated. We have shown for the first time that preincubation of the cells with the cyclooxygenase inhibitors, indomethacin and aspirin, or lipoxygenase inhibitors, nordihydroguaiaretic acid, caffeic acid and baicalein, almost completely prevents the intracellular Ca2+ concentration increase induced by glutoxim or molixan.

[The effect of glutoxim on Na+ transport in frog skin: the role of cytoskeleton].

Using voltage-clamp technique, the possible role of the cytoskeleton in the effect of pharmacological analogue of oxidized glutathione (GSSG), drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincibation of the skin with the microtubular disrupter, nocodazole, actin filament disrupter, cytochalasin D or protein phosphatase PP1/PP2A inhibitor, calyculin A, significantly decrease the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of microtubules and microfilaments in the regulatory effect of glutoxim on Na+ transport in frog skin and that reorganization of actin filaments or microtubules leads to inhibition of stimulatory effect of glutoxim on Na+ transport in frog skin epithelia.

[The involvement of actin cytoskeleton in glutoxim and molixan effect on intracellular Ca(2+)-concentration in macrophages].

Glutoxim and molixan belong to new generation of disulfide-containing drugs with immunomodulatory, hepatoprotective and hemopoetic effect on cells. Using Fura-2AM microfluorimetry, two structurally distinct actin filament disrupters, latrunculin B and cytochalasin D, and calyculin A, which causes actin filaments condensation under plasmalemma, we have shown the involvement of actin cytoskeleton in the intracellular Ca(2+)-concentration increase induced by glutoxim or molixan in rat peritoneal macrophages. Morphological data obtained with the use of rhodamine-phalloidine have demonstrated that glutoxim and molixan cause the actin cytoskeleton reorganization in rat peritoneal macrophages.

[Effect of arachidonic and other fatty acids on the intracellular calcium concentration and calcium signaling in peritoneal macrophages].

Effects of arachidonic and other fatty acids on the intracellular Ca2+ concentration ([Ca2+]i) in rat peritoneal macrophages was investigated. It has been shown that cis-polyunsaturated arachidonic and linoleic induce a significant and dose-dependent increase in [Ca2+]i, which is due to depletion of thapsigargin-sensitive Ca2+ store and to stimulation of Ca2+ entry from the extracellular medium. Pharmacological characteristics of Ca2+ entry induced by arachidonic acid appeared to be similar to those of store-dependent Ca2+ entry activated by thapsigargin or cyclopiazonic acid; Ca2+ entry is attenuated by the same Ca2+ channel inhibitors, by tyrosine kinase inhibitor genistein and epoxygenase inhibitor proadifen.

[The role of cytoskeleton structures in regulation of Ca2+ responses in macrophages].

The role of the cytoskeleton in regulation of purinergic agonist- and endoplasmic Ca(2+)-ATPase inhibitors-induced Ca2+ signals in rat peritoneal macrophages was investigated. It has been shown that in cells pretreated with agents that disrupt microtubules (vinblastine, colchicine, colcemid) or actin microfilaments (cytochalasins, phalloidin), the ability of thapsigargin or cyclopiazonic acid to empty Ca2+ stores and activate store-dependent Ca2+ influx was significantly attenuated. On the contrary, microfilaments and microtubule disrupters did not affect ATP- or UTP-induced Ca2+ mobilization, indicating that release of Ca2+ from intracellular stores through the inositol phosphate pathway was intact.

[Ca(2+)-signaling in peritoneal macrophages].

Mechanisms of the Ca2+ signal generation and regulation in peritoneal macrophages activated with purinergic agonists (ATP, UTP), as well as endoplasmic Ca(2+)-ATPase inhibitors, were investigated. Using a wide range of drugs affecting the intracellular signaling systems' components, an important role of second messenger systems and other key functional cellular systems in Ca2+ signals regulation in the macrophages, was shown.

[Role of protein kinase C in the regulation of Ca-responses induced by purinergic agonists and thapsigargin in rat peritoneal macrophages].

The effect of protein kinase C activating phorbol ester, phorbol-12-myristate-13-acetate (PMA), on purinergic agonists- and thapsigargin-induced Ca2+ signals in Fura-2 loaded rat peritoneal macrophages was investigated. PMA (100 ng/ml) was shown to inhibit 200 muM ATP- or 200 microM UTP-evoked Ca2+ entry in macrophages. Protein kinase C activation by PMA also inhibits the store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (0.

[Effect of inhibitors of mitochondrial oxidative metabolism on Ca-responses induced by purinergic agonists and thapsigargin in rat peritoneal macrophages].

Effects of two metabolic inhibitors, oligomycin and carbonyl cyanide m-fluorophenylhydrazone (FCCP), on Ca2+ signals induced by purinergic agonists and thapsigargin in Fura-2-loaded rat peritoneal macrophages was investigated. 1 microgram/ml oligomycin or 1 microM FCCP were shown to inhibit 200 microM ATP or 200 microM UTP-evoked Ca2+ entry in macrophages. Independently of their chemical structure and site of inhibition, both metabolic poisons also inhibit the store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (0.

[Organic and inorganic blockers of potential-dependent Ca2+ channels inhibit store-dependent entry of Ca2+ into rat peritoneal macrophages].

The effect of organic and inorganic blockers of voltage-dependent Ca(2+)-channels on thapsigargin- and UTP-induced store-operated Ca(2+)-entry in Fura-2-loaded rat peritoneal macrophages was investigated. This store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca(2+)-stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (0.5 microM) or purinergic agonist UTP (200 microM) is inhibited by the following pharmacological agents: two structurally distinct organic Ca(2+)-channel blockers nifedipine and verapamil; inorganic Ca(2+)-channel inhibitors Ni2+, La3+, Gd3+; nonselective cation channel blocker niflumic acid.

[Phenylarsine oxide, a tyrosine phosphatase inhibitor, induces an increase in the intracellular concentration of calcium in rat peritoneal macrophages and human fibroblasts].

Using Fura-2 microfluorimetry, phenylarsine oxide (PAO) (10-50 microM), a potent tyrosine phosphatase inhibitor, was shown to induce a dose-dependent increase in the free Ca2+ intracellular concentration in rat peritoneal macrophages and human foreskin fibroblasts. The PAO-induced increase in [Ca2+]i is not due presumably to depletion of intracellular Ca2+ stores but to mainly a stimulation of Ca2+ entry from the extracellular medium. This PAO-activated Ca2+ entry is attenuated by the following pharmacological agents.

[Effect of tyrosine kinase and tyrosine phosphatase inhibitors on ATP- and thapsigargin-induced CA2+ entry in rat peritoneal macrophages].

The effect of two structurally distinct tyrosine kinase inhibitors, genistein (100 microM) and methyl-2, 5-dihydroxycinnamate (25 microM) on ATP- and thapsigargin-induced Ca2+ signals in Fura-2-loaded rat peritoneal macrophages was investigated. Both compounds were shown to inhibit ATP-evoked Ca2+ entry but not to release from internal stores. Both compounds also inhibit the store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (100 nM).

[Creatine kinase activity in guinea pig tissues in experimental pseudotuberculosis].

Dynamics of creatine kinase activity was studied in heart muscle, liver tissue, lymphatic glands, intestine and spleen of guinea pigs infected with pseudotuberculosis microbes. The maximal increase in creatine kinase activity was observed in lymphatic glands and in heart muscle within the first day after the pseudotuberculosis infection. The enzymatic activity increase in liver tissue occurred within the fifth day, while in spleen--within twelfth day after pseudotuberculosis infection.