Antagonist effect of flufenamic acid on TRPM2 cation channels activated by hydrogen peroxide.

Abstract:

:The melastatin-related transient receptor potential channel TRPM2 is a plasma membrane Ca(2+)-permeable cation channel that is activated by hydrogen peroxide (H(2)O(2)) as a consequence of oxidative stress although the channel activation by H(2)O(2) 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 H(2)O(2) 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 H(2)O(2). 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 Ca(2+) and heavy metal ions. H(2)O(2) (10 mM) and FA (0.1 mM) were applied extracellularly. Non-selective cation currents were consistently induced by H(2)O(2). The time cause of H(2)O(2) effects was characterized by a delay of 2-5 min and a slow current induction to reach a plateau. The H(2)O(2)- 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 H(2)O(2)activated currents in CHO cells. FA in CHO cells may be considered, at best, a starting point for the development of TRPM2 channel blockers.

journal_name

Cell Biochem Funct

authors

Naziroğlu M,Lückhoff A,Jüngling E

doi

10.1002/cbf.1310

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

383-7

issue

4

eissn

0263-6484

issn

1099-0844

journal_volume

25

pub_type

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