Direct modulation of TRPM4 and TRPM3 channels by the phospholipase C inhibitor U73122Reportar como inadecuado




Direct modulation of TRPM4 and TRPM3 channels by the phospholipase C inhibitor U73122 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Reference: Leitner, MG, Michel, N, Behrendt, M et al., (2016). Direct modulation of TRPM4 and TRPM3 channels by the phospholipase C inhibitor U73122. British Journal of Pharmacology, 173 (16), 2555-2569.Citable link to this page:

 

Direct modulation of TRPM4 and TRPM3 channels by the phospholipase C inhibitor U73122

Abstract: BACKGROUND AND PURPOSE: Signalling through phospholipase C (PLC) controls many cellular processes. Much information on the relevance of this important pathway has been derived from pharmacological inhibition of the enzymatic activity of PLC. We found that the most frequently employed PLC inhibitor, U73122, activates endogenous ionic currents in widely used cell lines. Given the extensive use of U73122 in research, we set out to identify these U73122-sensitive ion channels. EXPERIMENTAL APPROACH: We performed detailed biophysical analysis of the U73122-induced currents in frequently used cell lines. KEY RESULTS: At concentrations required to inhibit PLC, U73122 modulated the activity of transient receptor potential melastatin (TRPM) channels through covalent modification. U73122 was shown to be a potent agonist of ubiquitously expressed TRPM4 channels and activated endogenous TRPM4 channels in CHO cells independently of PLC and of the downstream second messengers PI(4,5)P2 and Ca(2+) . U73122 also potentiated Ca(2) (+) -dependent TRPM4 currents in human Jurkat T-cells, endogenous TRPM4 in HEK293T cells and recombinant human TRPM4. In contrast to TRPM4, TRPM3 channels were inhibited whereas the closely related TRPM5 channels were insensitive to U73122, showing that U73122 exhibits high specificity within the TRPM channel family. CONCLUSIONS AND IMPLICATIONS: Given the widespread expression of TRPM4 and TRPM3 channels, these actions of U73122 must be considered when interpreting its effects on cell function. U73122 may also be useful for identifying and characterizing TRPM channels in native tissue, thus facilitating the analysis of their physiology.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Accepted ManuscriptDate of acceptance:15 June 2016Notes:Copyright © 2016 The British Pharmacological Society. This is the accepted manuscript version of the article. The final version is available online from Wiley at: https://doi.org/10.1111/bph.13538

Bibliographic Details

Publisher: Wiley

Publisher Website: http://onlinelibrary.wiley.com/

Journal: British Journal of Pharmacologysee more from them

Publication Website: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476-5381

Volume: 173

Issue: 16

Extent: 2555-2569

Issue Date: August 2016

pages:2555-2569Identifiers

Doi: https://doi.org/10.1111/bph.13538

Eissn: 1476-5381

Issn: 0007-1188

Uuid: uuid:47f68791-3d0a-4f13-9bc9-8b6307e7fb59

Urn: uri:47f68791-3d0a-4f13-9bc9-8b6307e7fb59

Pubs-id: pubs:690085 Item Description

Type: journal-article;

Language: eng

Version: Accepted ManuscriptKeywords: Journal Article

Relationships





Autor: Leitner, MG - - - Michel, N - - - Behrendt, M - - - Dierich, M - - - Dembla, S - - - Wilke, BU - - - Konrad, M - - - Lindner, M -

Fuente: https://ora.ox.ac.uk/objects/uuid:47f68791-3d0a-4f13-9bc9-8b6307e7fb59



DESCARGAR PDF




Documentos relacionados