Inhibition of store-operated calcium entry-mediated superoxide generation by histamine trifluoromethyltoluide independent of histamine receptors

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• 作者：Dong-Chan Kim ; So-Young Lee ; Dong-Jae Jun ; Sun-Hee Kim ; Jong-Hee Lee ; Eun-Mi Hur ; Nam-In Baek and Kyong-Tai Kim
• 关键词：SOCE ; Calcium ; HTMT ; Superoxide ; Inflammation
• 刊名：Biochemical Pharmacology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：70
• 期：11
• 页码：1613-1622
• 全文大小：381 K

文摘

Store-operated calcium entry (SOCE) plays an important role in shaping the Ca²⁺ 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 Ca²⁺ elevation without affecting Ca²⁺ release from intracellular stores. HTMT also inhibited TG-induced Ca²⁺ current and Ba²⁺/Mn²⁺ 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.