Inhibition of store-operated calcium entry-mediated superoxide generation by histamine trifluoromethyltoluide independent of histamine receptors.
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.
Kim
Dong-Chan
DC
Division of Molecular and Life Science, SBD-NCRC, Pohang University of Science and Technology, Pohang 790-784, POSTECH, San 31, Hyoja Dong, South Korea.
Lee
So-Young
SY
Jun
Dong-Jae
DJ
Kim
Sun-Hee
SH
Lee
Jong-Hee
JH
Hur
Eun-Mi
EM
Baek
Nam-In
NI
Kim
Kyong-Tai
KT
D002118:Calcium / Q000378:metabolism*; D018922:HL-60 Cells; D006632:Histamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D011968:Receptors, Histamine / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D020298:U937 Cells
D006633:Histamine Antagonists; D011968:Receptors, Histamine; C087869:histamine trifluoromethyl-toluidide; D013481:Superoxides; D006632:Histamine; D002118:Calcium