TY - JOUR
T1 - Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB)
AU - Togashi, K.
AU - Inada, H.
AU - Tominaga, M.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - 2-APB
KW - Insulin
KW - TRPM2
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U2 - 10.1038/sj.bjp.0707675
DO - 10.1038/sj.bjp.0707675
M3 - Article
C2 - 18204483
AN - SCOPUS:40949124783
VL - 153
SP - 1324
EP - 1330
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 6
ER -