Format

Send to:

Choose Destination
See comment in PubMed Commons below
Br J Pharmacol. 2008 Mar;153(6):1324-30. doi: 10.1038/sj.bjp.0707675. Epub 2008 Jan 21.

Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB).

Author information

  • 1Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.

Abstract

BACKGROUND AND PURPOSE:

Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca(2+)-permeable cation channel and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. TRPM2 current responses are reported to be drastically potentiated by the combination of each of these ligands with heat. Furthermore, the combination of cyclic ADP-ribose with heat also activates TRPM2. Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A(2) inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible.

EXPERIMENTAL APPROACH:

To facilitate future research on TRPM2, we screened several compounds to investigate their potential to activate or inhibit the TRPM2 channels using the patch-clamp technique in HEK293 cells, transfected with human TRPM2.

KEY RESULTS:

2-aminoethoxydiphenyl borate (2-APB) exhibited a rapid and reversible inhibition of TRPM2 channels that had been activated by its ADP-ribose or cADP-ribose and heat in a dose-dependent manner (IC(50) about 1 microM). 2-APB also inhibited heat-evoked insulin release from pancreatic islets, isolated from rats.

CONCLUSIONS AND IMPLICATIONS:

2-APB proved to be a powerful and effective tool for studying the function of TRPM2.

PMID:
18204483
[PubMed - indexed for MEDLINE]
PMCID:
PMC2275460
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Write to the Help Desk