Pharmacological profiling of the TRPV3 channel in recombinant and native assays

Background and Purpose Transient receptor potential vanilloid subtype 3 (TRPV3) is implicated in nociception and certain skin conditions. As such, it is an attractive target for pharmaceutical research. Understanding of endogenous TRPV3 function and pharmacology remains elusive as selective compound...

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Bibliographic Details
Published in:	British journal of pharmacology 2014-05, Vol.171 (10), p.2631-2644
Main Authors:	Grubisha, Olivera, Mogg, Adrian J, Sorge, Jessica L, Ball, Laura‐Jayne, Sanger, Helen, Ruble, Cara L A, Folly, Elizabeth A, Ursu, Daniel, Broad, Lisa M
Format:	Article
Language:	eng
Subjects:	Animals Calcium Signaling - drug effects Dose-Response Relationship, Drug FLIPR HEK293 Cells Humans Ligands Medical research Membrane Transport Modulators - pharmacology Mice mouse 308 keratinocytes Pharmacology Rats Recombinant Proteins - drug effects Recombinant Proteins - metabolism Themed Section: The Pharmacology of Trp Channels Transfection TRP channel TRPV Cation Channels - drug effects TRPV Cation Channels - genetics TRPV Cation Channels - metabolism TRPV3
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Summary:	Background and Purpose Transient receptor potential vanilloid subtype 3 (TRPV3) is implicated in nociception and certain skin conditions. As such, it is an attractive target for pharmaceutical research. Understanding of endogenous TRPV3 function and pharmacology remains elusive as selective compounds and native preparations utilizing higher throughput methodologies are lacking. In this study, we developed medium‐throughput recombinant and native cellular assays to assess the detailed pharmacological profile of human, rat and mouse TRPV3 channels. Experimental Approach Medium‐throughput cellular assays were developed using a Ca2+‐sensitive dye and a fluorescent imaging plate reader. Human and rat TRPV3 pharmacology was examined in recombinant cell lines, while the mouse 308 keratinocyte cell line was used to assess endogenous TRPV3 activity. Key Results A recombinant rat TRPV3 cellular assay was successfully developed after solving a discrepancy in the published rat TRPV3 protein sequence. A medium‐throughput, native, mouse TRPV3 keratinocyte assay was also developed and confirmed using genetic approaches. Whereas the recombinant human and rat TRPV3 assays exhibited similar agonist and antagonist profiles, the native mouse assay showed important differences, namely, TRPV3 activity was detected only in the presence of potentiator or during agonist synergy. Furthermore, the native assay was more sensitive to block by some antagonists. Conclusions and Implications Our findings demonstrate similarities but also notable differences in TRPV3 pharmacology between recombinant and native systems. These findings offer insights into TRPV3 function and these assays should aid further research towards developing TRPV3 therapies. Linked Articles This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
ISSN:	0007-1188 1476-5381