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

Br J Pharmacol. 2008 Mar;153(6):1324-30. doi: 10.1038/sj.bjp.0707675. Epub 2008 Jan 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Animals
  • Antifungal Agents / pharmacology
  • Boron Compounds / administration & dosage
  • Boron Compounds / pharmacology*
  • Cell Line
  • Cinnamates / pharmacology
  • Cyclic ADP-Ribose / metabolism
  • Dose-Response Relationship, Drug
  • Flufenamic Acid / pharmacology
  • Hot Temperature
  • Humans
  • In Vitro Techniques
  • Inhibitory Concentration 50
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • TRPM Cation Channels / antagonists & inhibitors*
  • Transfection
  • ortho-Aminobenzoates / pharmacology


  • Antifungal Agents
  • Boron Compounds
  • Cinnamates
  • Insulin
  • TRPM Cation Channels
  • TRPM2 protein, human
  • ortho-Aminobenzoates
  • 4-amylcinnamoylanthranilic acid
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • Flufenamic Acid
  • 2-aminoethoxydiphenyl borate