Display options
Cite
Bluhm Y, Raudszus R, Wagner A, et al. Valdecoxib blocks rat TRPV2 channels. Eur J Pharmacol. 2021;174702doi: 10.1016/j.ejphar.2021.174702.
Bluhm, Y., Raudszus, R., Wagner, A., Urban, N., Schaefer, M., & Hill, K. (2021). Valdecoxib blocks rat TRPV2 channels. European journal of pharmacology, 174702. https://doi.org/10.1016/j.ejphar.2021.174702
Bluhm, Yannik, et al. "Valdecoxib blocks rat TRPV2 channels." European journal of pharmacology vol. (2021): 174702. doi: https://doi.org/10.1016/j.ejphar.2021.174702
Bluhm Y, Raudszus R, Wagner A, Urban N, Schaefer M, Hill K. Valdecoxib blocks rat TRPV2 channels. Eur J Pharmacol. 2021 Dec 14;174702. doi: 10.1016/j.ejphar.2021.174702. Epub 2021 Dec 14. PMID: 34919887.
Copy Download .nbib Format: NLM
Share it on

Eur J Pharmacol. 2021 Dec 14;174702. doi: 10.1016/j.ejphar.2021.174702. Epub 2021 Dec 14.

Valdecoxib blocks rat TRPV2 channels.

European journal of pharmacology

Yannik Bluhm, Rick Raudszus, Anne Wagner, Nicole Urban, Michael Schaefer, Kerstin Hill

Affiliations

  1. Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Härtelstr. 16-18, 04107, Leipzig, Germany.
  2. Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Härtelstr. 16-18, 04107, Leipzig, Germany. Electronic address: [email protected].

PMID: 34919887 DOI: 10.1016/j.ejphar.2021.174702

Abstract

The transient receptor potential vanilloid 2 (TRPV2) channel is broadly expressed in a multitude of different tissues and is implicated in the pathology of several diseases, such as the progression of different cancer types. However, a lack of specific, potent and non-toxic TRPV2 activators and inhibitors complicate further studies to clarify the role of TRPV2. We here present valdecoxib as a novel inhibitor of heterologously expressed rat TRPV2 channels in HEK293 cells and native TRPV2 channels, endogenously expressed in the rat basophilic leukemia (RBL-2H3) cell line. Fluorometric assays reveal an IC50 of 9 μM and 11 μM for TRPV2 in HEK293 and RBL-2H3 cells, respectively. Closely related TRPV1, TRPV3 or TRPV4 channels are not blocked by valdecoxib. The inhibition is reversible and direct as confirmed by whole-cell and excised inside-out electrophysiological recordings. Other cyclooxygenase-2 inhibitors do not affect TRPV2 activity. Furthermore, we demonstrate that the combined application of 2-aminoethoxydiphenyl borate (2-APB) and probenecid at concentrations, which, on their own, elicit only small TRPV2 currents, act in a highly synergistic manner when applied simultaneously. Taken together, we here provide novel tools and chemical lead structures for further studying TRPV2 channel function in native tissues.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Electrophysiology; Fluorometric calcium assays; TRPV2; Valdecoxib

Conflict of interest statement

Declaration of competing interest None.

Publication Types