Skip to Main content Skip to Navigation
Journal articles

Pharmacological characterization and molecular determinants of the activation of transient receptor potential V2 channel orthologs by 2-aminoethoxydiphenyl borate.: 2APB as a tool to study TRPV2 pharmacology and function

Abstract : Despite its expression in different cell types, transient receptor potential V2 (TRPV2) is still the most cryptic members of the TRPV channel family. 2-Aminoethoxydiphenyl borate (2APB) has been shown to be a common activator of TRPV1, TRPV2, and TRPV3, but 2APB-triggered TRPV2 activation remains to be thoroughly characterized. In this study, we have developed an assay based on cell lines stably expressing mouse TRPV2 channels and intracellular calcium measurements to perform a pharmacological profiling of the channel. Phenyl borate derivatives were found to activate mouse TRPV2 with similar potencies and thus were used to screen a panel of channel blockers. Besides the classic TRP inhibitors ruthenium red (RR) and 1-(beta-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365), two potassium channel blockers, tetraethylammonium (TEA) and 4-aminopyridine, and an inhibitor of capacitative calcium entry, 1-(2-(trifluoromethyl) phenyl) imidazole (TRIM), were found to inhibit TRPV2 activation by 100 microM 2APB. Activation by 300 microM 2APB, however, could only be inhibited by RR and TRIM. Electrophysiological recordings demonstrated that TEA inhibition was use-dependent, suggesting that high concentrations of 2APB might induce a progressive conformational change of the channel. Comparison of TRPV2 orthologs revealed that the human channel was insensitive to 2APB. Analysis of chimeric constructs of mouse and human TRPV2 channels showed that the molecular determinants of 2APB sensitivity could be localized to the intracellular amino and carboxyl domains. Finally, using lentiviral-driven expression, we demonstrate that hTRPV2 exerts a dominant-negative effect on 2APB activation of native rodent TRPV2 channels and thus may provide an interesting tool to investigate cellular functions of TRPV2 channels.
Document type :
Journal articles
Complete list of metadatas

Cited literature [28 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00320694
Contributor : Francois Rassendren <>
Submitted on : Thursday, September 11, 2008 - 2:51:35 PM
Last modification on : Tuesday, November 5, 2019 - 12:38:01 PM
Long-term archiving on: : Saturday, November 26, 2016 - 12:59:28 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Véronique Juvin, Aubin Penna, Jean Chemin, Yea-Lih Lin, François-A Rassendren. Pharmacological characterization and molecular determinants of the activation of transient receptor potential V2 channel orthologs by 2-aminoethoxydiphenyl borate.: 2APB as a tool to study TRPV2 pharmacology and function. Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2007, 72 (5), pp.1258-68. ⟨10.1124/mol.107.037044⟩. ⟨inserm-00320694⟩

Share

Metrics

Record views

293