Amitriptyline Attenuates Ca2+ Responses Induced by Glutoxim and Molixan in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist, tricyclic antidepressant amitriptyline, significantly inhibits glutoxim- and molixan-induced Ca2+-responses in rat peritoneal macrophages. The results suggest possible involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca2+ concentration increase in macrophages.

Sigma-1 Receptor Antagonist Haloperidol Attenuates Store-Dependent Ca2+ Entry in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that preincubation of macrophages with sigma-1 receptor antagonist haloperidol leads to a significant inhibition of the store-dependent Ca2+ entry induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin or cyclopiazonic acid in rat peritoneal macrophages. The results suggest the involvement of the sigma-1 receptor in the regulation of storedependent Ca2+ entry in macrophages.

Phospholipase A2 Inhibitors Modulate the Effect of Trifluoperazine on the Intracellular Ca2+ Concentration in Macrophages.

Using Fura-2AM microfluorimetry, it was shown for the first time that phospholipase A2 inhibitors 4-bromophenacyl bromide and glucocorticosteroids prednisolone and dexamethasone attenuate Ca2+ responses induced by neuroleptic trifluoperazine in macrophages. The results suggest the involvement of phospholipase A2 and arachidonic acid metabolism cascade in the effect of trifluoperazine on intracellular Ca2+ concentration in macrophages.

Trifluoperazine Attenuates Store-Dependent Ca2+ Entry in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that preincubation of macrophages with the calsequestrin inhibitor neuroleptic trifluoperazine leads to a significant inhibition of the store-dependent Ca2+ entry induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin or cyclopiazonic acid in rat peritoneal macrophages. The results suggest calsequestrin involvement in the regulation of the store-dependent Ca2+ entry in macrophages.

The effect of chlorpromazine on intracellular Ca2+ concentration in macrophages.

Using Fura-2AM microfluorimetry, it was shown for the first time that neuroleptic chlorpromazine causes intracellular Ca2+ concentration increase in macrophages due to Ca2+ mobilization from intracellular Ca2+ stores and subsequent Ca2+ entry from the external medium. Chlorpromazine-induced Ca2+ entry is inhibited by La3+ and 2-aminoethoxydiphenyl borate and is associated with Ca2+ store depletion.

Methyl-ß-cyclodextrin modulates thapsigargin-induced store-dependent Ca2+ entry in macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that preincubation of macrophages with methyl-ß-cyclodextrin, inducing cholesterol extraction from membranes and raft disruption, leads to significant inhibition of thapsigargin-induced store-dependent Ca2+ entry in rat peritoneal macrophages. In contrast, macrophage treatment with methyl-ß-cyclodextrin after Ca2+ entry mechanisms were activated by store depletion by thapsigargin application leads to potentiation of subsequent store-dependent Ca2+ entry. The results suggest that intact lipid rafts are necessary for the activation but not the maintenance of store-dependent Ca2+ entry in macrophages.

Sigma-1 receptor antagonist haloperidol attenuates Ca2+ responses induced by glutoxim and molixan in macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor antagonist, antipsychotic haloperidol, significantly inhibits glutoxim- and molixan-induced Ca2+-response in peritoneal macrophages. These results indicate possible involvement of sigma-1 receptors in the signal cascade induced by glutoxim or molixan and leading to intracellular Ca2+ concentration increase in macrophages.

Methyl-ß-cyclodextrin inhibits Ca2+-responses induced by glutoxim and molixan in macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that methyl-ß-cyclodextrin, inducing cholesterol extraction from membranes and raft disruption, significantly inhibits glutoxim- and molixan-induced Ca2+-responses in rat peritoneal macrophages. The results suggest that intact rafts are necessary for signaling cascade induced by glutoxim or molixan and leading to intracellular Ca2+ concentration increase in macrophages.

[THE EFFECT OF EPOXYGENASE INHIBITORS ON Ca(2+)-RESPONSES INDUCED BY GLUTOXIM AND MOLIXAN IN MACROPHAGES].

Using Fura-2AM microfluorimetry the possible involvement of epoxygenase pathway of arachidonic acid metabolism in the effect of glutoxim and molixan on intracellular Ca2+ concentration in rat peritoneal macrophages was investigated. It was shown for the first time that preincubation of the macrophages with epoxygenase inhibitors, proadifen and econazole, significantly decreases the intracellular Ca2+ concentration increase induced by glutoxim and molixan. The addition of the epoxygenase inhibitors during the already developed store-dependent Ca(2+)-entry induced by glutoxim or molixan partially inhibits Ca(2+)-entry. The obtained data suggest the involvement of the products and/or enzymes of epoxygenase pathway of the arachidonic acid metabolism in the glutoxim and molixan effect on the Ca2+ signaling processes in macrophages.

Involvement of the Arp2/3 complex and WASP proteins in the effect of glutoxim and molixan on intracellular Ca(2+) concentration in macrophages.

The Fura-2AM fluorescent Ca(2+) probe was used to study the possibility that the Arp2/3 complex and WASP proteins are involved in the effects of glutoxim and molixan on the intracellular Ca(2+) concentration in macrophages. It has been demonstrated that preincubation of macrophages with inhibitors of the Arp2/3 complex or WASP proteins (CK-0944666 or wiskostatin, respectively) results in a significant suppression of Ca(2+)-responses induced by glutoxim or molixan. This suggests that polymerization of actin filaments is a process involved in the effect of glutoxim or molixan on intracellular Ca(2+) concentration 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 obtained data indicate the involvement of products and/or enzymes of the arachidonic acid cyclooxygenase and lipoxygenase metabolism pathways in the effect of glutoxim and molixan on the processes of Ca2+ signaling in macrophages.

[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.

[Microtubular disrupter nocodazole and vesicular transport inhibitor brefeldin A attenuate the glutoxim effect on Na+ transport in frog skin].

Using the voltage-clamp technique, a possible role of microtubules and vesicular transport in the effect of pharmacological analogue of oxidized glutathione, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that the disrupter of microtubules nocodazole or inhibitor of vesicular transport brefeldin A similarly modulate (completely inhibit) the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of reorganization of microtubules and vesicular transport in the regulatory effect of glutoxim on Na+ transport. .

[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 tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione and glutoxim on Na+ transport in frog skin].

Using voltage-clamp technique, the role of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione (GSSG) and its pharmacological analogue, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincubation of the skin with tyrosine kinase inhibitor genistein or with two structurally distinct phosphatidylinositol kinase inhibitors, wortmannin and LY294002, significantly decreased the stimulatory effect of GSSG or glutoxim on Na+ transport. The data suggest that GSSG and glutoxim might transactivate insulin receptor in the basolateral membrane of epithelial cells and trigger the signaling cascade, involving tyrosine kinases and phosphatidylinositol kinases, which lead to Na+ transport stimulation in frog skin.

[Phenylarsine oxide, a tyrosine phosphatase inhibitor, induces an increase in the intracellular concentration of calcium in rat peritoneal macrophages and human fibroblasts]. / Ingibitor tirozinfosfataz fenilarzinoksid indutsiruet uvelichenie vnutrikletochnoi kontsentratsii Ca2+ v peritoneal'nykh makrofagakh krysy i fibroblastakh cheloveka.

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. Organic and inorganic Ca2+ channel blockers: (nifedipine, verapamil and Ni2+); nonselective cation channel blocker niflumic acid; tyrosine kinase inhibitors genistein and methyl-2,5-dihydroxycinnamate; SH-reagents dithiothreitol parachloromercuribenzoate and N-ethylmaleimide; arachidonic acid metabolism inhibitors 4-bromophenacyl bromide, indomethacin and caffeic acid; microtubule disrupters vinblastine, colchicine and colcemide. On the contrary, microfilament disrupters, cytochalasin B and phalloidin, enhance PAO-activated Ca2+ entry. Our data suggest that the dynamic balance between tyrosine kinase and phosphatase activity may play a central role in the maintenance of homeostatic levels of [Ca2+]i both in unstimulated cells and after agonist application.

[The effect of docosatrienoic acid on the potassium channels of outward rectification in the membrane of rat peritoneal macrophages]. / Vliianie dokozatrienovoi kisloty na kalievye kanaly vykhodiashchego vypriamleniia v membrane peritoneal'nykh makrofagov krysy.

Application of docosatrienic acid was shown to dose-dependently decrease the peak K+ current amplitide and accelerate the potassium activation and inactivation kinetics at all membrane potentials. The data obtained suggests a direct effect of docosatrienic acid on the K+ channels in peritoneal macrophages.