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

K. Togashi, H. Inada, M. Tominaga

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

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 μM). 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.

Original languageEnglish
Pages (from-to)1324-1330
Number of pages7
JournalBritish Journal of Pharmacology
Volume153
Issue number6
DOIs
Publication statusPublished - 2008 Mar
Externally publishedYes

Keywords

  • 2-APB
  • Insulin
  • TRPM2

ASJC Scopus subject areas

  • Pharmacology

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