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

Abstract

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 ill a significant inhibition of subsequent TGinduced 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 HI 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. (c) 2005 Elsevier Inc. All rights reserved.