ABSTRACT
The early changes of electrophoretic mobility (EPM) of murine T lymphocytes induced by structural analogues of amixine-dihydrochloryde 4,4'-bis-[2(diethylamino)ethoxy]diphenyl (compound 1) and dihydrochloryde 2-methoxycarbonil-4,4'-bis-[2(diethylamino)ethoxy]diphenyl (compound 2) were studied by electrophoresis technique. During the interval 0-2 hours all compounds increased the absolute values of EPM in comparison with control. These changes were of the same kind--distinctions were quantitative. Amixine and compound 1 during the interval 2-4 hours additionally increased the EPM. The compound 2, on the contrary, decreased the EPM. It was shown that the opposite effects of the aforementioned compounds were caused by the fact that amixine and compound 1 induce, and compound 2 does not induce IFN production in T lymphocytes in vitro. The results of our experiments are important for understanding of the mechanisms of immunomodulating effect of amixine and its structural analogues.
Subject(s)
Biphenyl Compounds/pharmacology , Immunologic Factors/pharmacology , Spleen/drug effects , T-Lymphocytes/drug effects , Tilorone/pharmacology , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Electrophoresis , Interferons/agonists , Interferons/metabolism , Male , Mice , Mice, Inbred CBA , Spleen/cytology , T-Lymphocytes/cytology , Tilorone/analogs & derivativesABSTRACT
The amixine-induced early changes in the electrophoretic mobility (EPM) of murine splenic T lymphocytes were studied in vitro by the microelectrophoresis technique. It has been found that T lymphocytes treated with amixine have a greater EPM within the first hours of amixine addition than control cells. This change in EPM depends on the concentration of amixine in the medium and the duration ofamixine exposure. It was concluded that the amixine-treated cells have a greater net negative surface charge density than control cells. This effect may play an important role in the cell-cell interaction during the immune response.
Subject(s)
Interferon Inducers/pharmacology , Spleen/drug effects , T-Lymphocytes/drug effects , Tilorone/pharmacology , Animals , Cell Movement/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Electrophoresis , Male , Membrane Potentials/drug effects , Mice , Mice, Inbred CBA , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunologyABSTRACT
Alpha/beta-Interferon (alpha/beta-IFN)-induced early changes in the electrophoretic mobility (EPM) of murine splenic T lymphocytes were studied by the microelectrophoresis technique. It has been found that alpha/beta-IFN-treated T lymphocytes have a greater EPM than control cells within first hours of alpha/beta-IFN addition. This change in EPM depends on the concentration of alpha/beta-IFN in the medium and the duration of alpha/beta-IFN interaction with the cells. It is concluded that the alpha/beta-IFN-treated cells have a greater net negative charge of the cell surface than control cells.
Subject(s)
Interferon-alpha/pharmacology , Interferon-beta/pharmacology , T-Lymphocytes/drug effects , Animals , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Movement/physiology , Cells, Cultured , Dose-Response Relationship, Drug , Electrophoresis , Mice , Mice, Inbred CBA , Receptors, Cell Surface/metabolism , Spleen/cytology , Surface Properties , T-Lymphocytes/metabolism , T-Lymphocytes/physiology , Time FactorsABSTRACT
Complex processing and integration of the signals observed in neurons are facilitated by a diverse range ofthe gating properties of the ion channels in this cell type, particularly of the voltage-gated potassium channels. A distinctive combination of potassium channels endows neurons with a broad repertoire of the excitable properties and allows each neuron to respond in a specific manner to a given input at a given time. The properties of many potassium channels can be modulated by second messenger pathways activated by neurotransmitters and other stimuli. Potassium channels are among the most frequent targets of the actions of several signaling systems.
Subject(s)
Brain/physiology , Neurons/physiology , Potassium Channels/physiology , Animals , Brain/metabolism , Electrophysiology , Humans , Neurons/metabolism , Neurotransmitter Agents/metabolism , Potassium Channels/metabolism , Second Messenger Systems/physiologyABSTRACT
The complex processing and integration of signals observed in neurons are facilitated by the diverse range of gating properties of the ion channels in this cell type, particularly the voltage-gated K+ channels (Kv). A distinctive combination of K+ channels endows neurons with a broad repertoire of excitable properties and allows each neuron to respond in a specific manner to a given input at a given time. The properties of many K+ channels can be modulated by second messenger pathways activated by neurotransmitters and other stimuli. K+ channels are among the most frequent targets of the actions of several signalling systems.
Subject(s)
Ion Channel Gating/physiology , Neurons/metabolism , Potassium Channels, Voltage-Gated/metabolism , Potassium/metabolism , Animals , Culture Media , Ion Channel Gating/drug effects , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neurons/physiology , PC12 Cells , Potassium Channels, Voltage-Gated/physiology , Rats , Tetraethylammonium/pharmacologyABSTRACT
Neuronal responses to hypoxia-ischemia can be acute or chronic. In the early stages neuronal responses to ischemia-hypoxia are dependent on the modulation of ion channels. Acute responses relay mainly on O2-regulated ion channels which mediate adaptive changes in neuron excitability. Energy failure, an early consequence of hypoxia-ischemia, causes disruption of ionic homeostasis and accumulation of extracellular neurotransmitters. NMDA and AMPA/kainate receptors and Ca2+ channels contribute to excitotoxic neuronal degeneration. Excitotoxicity leads to increased Ca2+ influx, which can activate cytotoxic intracellular pathways. Reactive oxygen species (oxygen free radicals) generated during ischemia-reperfusion contribute to the injury. Oxygen free-radicals serve as important signalling molecules that trigger inflammation and apoptosis. Excitatory amino acid-receptor antagonists and Ca2+ channels blockers can provide neuroprotection in experimental models of hypoxia-ischemia but disrupt normal brain function. Because of their relative lack of behavioral side-effects, voltage-dependent Na+ channels blockers may have advantage over other neuroprotective mechanisms. The blockade of voltage-gated Na+ channels reduces the excitability of neurons, Na+ influx and the accumulation of intracellular Na+. These improve the ionic homeostasis and cellular energy levels and prevent ischemia-hypoxia induced neuronal injury and neuronal damage mediated by Ca2+ overload.
Subject(s)
Brain Ischemia/pathology , Hypoxia, Brain/pathology , Neuroprotective Agents/pharmacology , Reperfusion Injury/prevention & control , Animals , Brain Ischemia/metabolism , Calcium/metabolism , Calcium Channels/metabolism , Excitatory Amino Acid Antagonists/pharmacology , Humans , Hypoxia, Brain/metabolism , Ion Channels/metabolism , Kainic Acid/metabolism , Nerve Degeneration/pathology , Neurons/drug effects , Neurons/metabolism , Oxygen/metabolism , Reactive Oxygen Species/metabolism , Receptors, Glutamate/drug effects , Receptors, Glutamate/metabolism , Reperfusion Injury/metabolism , Sodium/metabolism , Sodium Channel Blockers/pharmacology , Sodium Channels/drug effects , Sodium Channels/metabolismABSTRACT
The action of pharmacological drugs (caffeine, procaine, ruthenium red) which influenced the release of Ca2+ from endoplasmatic reticulum, the electrical responses of dog pancreatic acinar cells was investigated using intracellular glass microelectrodes. These drugs were used to elucidate the mechanisms of Ca2+ release from endoplasmatic reticulum. Membrane depolarization and decrease of input resistance were observed in the presence of caffeine. Procaine and ruthenium red suppressed electrical responses of acinar cells to caffeine. The results obtained permit supposing that there are two mechanisms of Ca2+ release from intracellular stores in pancreatic acinar cells: Ca(2+)-induced one and using inositol-1,4,5-triphosphate.
