Inhibition of store-operated calcium entry-mediated superoxide generation by histamine trifluoromethyltoluide independent of histamine receptors |
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Authors: | Kim Dong-Chan Lee So-Young Jun Dong-Jae Kim Sun-Hee Lee Jong-Hee Hur Eun-Mi Baek Nam-In Kim Kyong-Tai |
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Affiliation: | Division of Molecular and Life Science, SBD-NCRC, Pohang University of Science and Technology, Pohang 790-784, POSTECH, San 31, Hyoja Dong, South Korea. |
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Abstract: | Store-operated calcium entry (SOCE) plays an important role in shaping the Ca(2+) response of various tissues and cell types. In this report, we show that thapsigargin (TG)-induced SOCE was inhibited by the histamine receptor agonist, histamine-trifluoromethyltoluide (HTMT), in U937 and HL-60 human promyelocytes. Preincubation of HTMT resulted in a significant inhibition of subsequent TG-induced Ca(2+) elevation without affecting Ca(2+) release from intracellular stores. HTMT also inhibited TG-induced Ca(2+) current and Ba(2+)/Mn(2+) influx in a concentration-dependent manner. In contrast with HTMT, other H1 histamine receptor agonists, histamine, 2-methylhistamine and 2-thiazolylethylamine, did not affect TG-induced SOCE. In addition, HTMT also attenuated TG-induced cytosolic superoxide generation. Taken together, our data clearly suggest that the anti-inflammatory effect of HTMT may occur through direct inhibition of SOCE. |
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Keywords: | [Ca2+]i cytosolic calcium ion concentration Fura-2/AM fura-2 penta acetoxymethyl ester H1R histamine 1 receptor HTMT histamine trifluoromethyltoluide SOCE store-operated Ca2+ entry |
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