Na+/Ca2+ exchange inhibitors modulate thapsigargin-induced Ca2+ and Na+ influx in human lymphocytes |
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Authors: | J. R. Nofer E. Pulawski R. Junker U. Seedorf G. Assmann W. Zidek M. Tepel |
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Affiliation: | 1. Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westf?lische Wilhelms-Universit?t, Albert Schweizer Strasse 33, D-48149, Münster, Germany 2. Institut für Arterioskleroseforschung an der Universit?t Münster, Domagkstrasse 3, D-48149, Münster, Germany 3. Ruhr-Universit?t Bochum, Universit?tsklinik Marienhospital, H?lkeskampring 40, Herne, Germany
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Abstract: | Thapsigargin has been shown the elevate intracellular Na(+) concentration in human lymphocytes, but mechanisms underlying thapsigargin-induced Na(+) entry are little understood. In the present study we investigated thapsigargin-induced changes in cytosolic free Na(+) and Ca(2+) concentration in human lymphocytes after inhibition of the Na(+)/Ca(2+) exchange with two structurally unrelated compounds, dimethylthiourea ad bepridil. The intracellular Na(+) increase induced by 5 microM thapsigargin was significantly enhanced in the presence of 5 mM dimethylthiourea or 40 microM bepridil. In contrast, both compounds significantly decreased the thapsigargin-induced intracellular Ca(2+) elevation. No effect of dimethylthiourea or bepridil on thapsigargin-induced Ca(2+) influx was observed in the absence of extracellular Na(+). These observations are consistent with the hypothesis that thapsigargin stimulates Na(+)/Ca(2+ )exchange in human lymphocytes. However, Na(+)/Ca(2+) exchange does not mediate Na(+) influx in human lymphocytes. |
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Keywords: | Na+/Ca2+ exchange Na+ influx Ca2+ influx Thapsigargin |
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