Effect of cytochalasins on cytosolic-free calcium concentration and phosphoinositide metabolism in leukocytes |
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Authors: | Susan Treves Francesco Di Virgilio Giorgina M. Vaselli Tullio Pozzan |
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Affiliation: | 1. N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina str., 4, 119334 Moscow, Russia;2. N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, Russia;3. Talrose Institute for Energy Problems of Chemical Physics, Semenov Federal Center of Chemical Physic, Russian Academy of Sciences, Moscow, Russia;4. Skolkovo Institute of Science and Technology, Skolkovo, Russia;1. Department of Physiology, Semmelweis University Medical School, Budapest, Hungary;2. Laboratory of Molecular Physiology, Hungarian Academy of Sciences, Budapest, Hungary;3. Institute of Neuroscience, Italian National Research Council, Padova, Italy;4. Venetian Institute of Molecular Medicine, Padova, Italy |
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Abstract: | Cytochalasins are routinely used to stimulate a variety of functions in eukaryotic cells even though their precise mode of action remains to be elucidated. In the present work we used the fluorescent Ca2+ indicator quin2 to study the effect of various cytochalasins, cytochalasins A, B, C, D, E (CA, CB, CC, CD, CE) and dihydrocytochalasin B (dhCB) on the intracellular Ca2+ concentration ([Ca2+]i) in various types of leukocytes, viz, neutrophils and lymphocytes. In human neutrophils, cytochalasins increase [Ca2+]i mainly by releasing Ca2+ from membrane-bound, intracellular stores. Thus, in order to readily appreciate the effect of cytochalasins on [Ca2+ )i, these cells must be loaded with low intracellular quin2 concentrations. On the other hand, in peripheral blood lymphocytes, splenocytes and thymocytes, the increase in [Ca2+]i is predominantly due to an increased Ca2+ influx from the extracellular medium. In addition, we found that in neutrophils these drugs prolong the increase in [Ca2+]i induced by chemotactic peptides, probably by increasing the cell permeability to Ca2+. Finally, in thymocytes, cytochalasins potentiate the production of inositol phosphates induced by the polyclonal mitogen concanavalin A (conA). |
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