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- Title
Antagonist effect of flufenamic acid on TRPM2 cation channels activated by hydrogen peroxide.
- Authors
Nazıroğlu, Mustafa; Lückhoff, Andreas; Jüngling, Eberhard
- Abstract
The melastatin-related transient receptor potential channel TRPM2 is a plasma membrane Ca2+-permeable cation channel that is activated by hydrogen peroxide (H2O2) as a consequence of oxidative stress although the channel activation by H2O2 appears to represent a cell-specific process in cells with endogenous expression of TRPM2. Flufenamic acid (FA) is a non-steroidal anti-inflammatory compound. Whether H2O2 activates or FA inhibits TRPM2 channels in Chinese hamster ovary (CHO) cell is currently unknown. Due to lack of known antogonists of this channel, we demonstrate in CHO cells that FA inhibits TRPM2 activated by extracellular H2O2. CHO cells were transfected with cDNA coding for TRPM2. Cells were studied with the conventional whole-cell patch clamp technique. The intracellular solution used EDTA (10 mM) as chelator for Ca2+ and heavy metal ions. H2O2 (10 mM) and FA (0.1 mM) were applied extracellularly. Non-selective cation currents were consistently induced by H2O2. The time cause of H2O2 effects was characterized by a delay of 2-5 min and a slow current induction to reach a plateau. The H2O2- induced inward current was effectively inhibited by 0.1 mM FA applied extracellularly. In conclusion, we have demonstrated that FA is an effective antogonist of TRPM2 channels and H2O2activated currents in CHO cells. FA in CHO cells may be considered, at best, a starting point for the development of TRPM2 channel blockers. Copyright © 2006 John Wiley & Sons, Ltd.
- Publication
Cell Biochemistry & Function, 2007, Vol 25, Issue 4, p383
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.1310