S. N. Butov

The effect of chlorpromazine on intracellular Ca 2+ 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-β-cyclodextrin inhibits Ca(2+)-responses induced by glutoxim and molixan in macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that methyl-β-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.

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 Ranatemporaria 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 the voltage-clamp technique, the possible implication of cytoskeleton in the effect of glutoxim, a pharmacological analog of oxidized glutathione (GSSG), on Na+ transport in the skin of frog Rana temporaria was investigated. It was shown for the first time that skin preincubation with nocodazole, a microtubular disrupter; cytochalasin D, actin filament disrupter; or protein phosphatase PP1/PP2A inhibitor calyculin A significantly decreased the stimulatory effect of glutoxim on Na+ transport. The results 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 the stimulatory effect of glutoxim on Na+ transport in frog skin epithelia.

Involvement of tyrosine and phosphatidylinositol kinases in oxidized glutathione and glutoxim regulation of Na+ transport in frog skin

The role of tyrosine and phosphatidylinositol kinases in oxidized glutathione (GSSG) and its pharmacological analogue, glutoxim, regulation of Na+ transport in Rana temporaria frog skin was investigated by the voltage-clamp technique. It was shown for the first time that the 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 can transactivate insulin receptor in the basolateral membrane of epithelial cells and trigger the signaling cascade, which involves tyrosine and phosphatidylinositol kinases, which stimulates Na+ transport in frog skin.

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.

Sigma-1 Receptor Antagonist Haloperidol Attenuates Store-Dependent Ca 2+ 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.

Inhibitors of the Metabolism of Arachidonic Acid Suppress Ca2+ Responses Induced by Trifluoperazine in Macrophages

The influence of the neuroleptic trifluoperazine on the intracellular concentration of Ca2+ in macrophages of rats was studied using a Fura-2AM fluorescent Ca2+ probe. It was found that trifluoperazine causes a dose-dependent increase in the intracellular Ca2+ concentration associated with Ca2+ mobilization from intracellular Ca2+ stores and subsequent entry of Ca2+ into peritoneal macrophages of rats. It was also shown that inhibitors of phospholipase A2 (4-bromophenacyl bromide, prednisolone, and dexamethasone), cyclooxygenases (aspirin and indomethacin), and lipoxygenases (caffeic acid, zileuton, and baicalein) suppress Ca2+ responses induced by trifluoperazine in macrophages. The data obtained indicate the participation of enzymes and/or products of the cascade of arachidonic acid metabolism in the influence of trifluoperazine on the intracellular concentration of Ca2+ in peritoneal 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.