A critical evaluation of TRPA1-mediated locomotor behavior in zebrafish as a screening tool for novel anti-nociceptive drug discovery

Scientific Reports
Mee Jung KoRichard M van Rijn

Abstract

Current medications inadequately treat the symptoms of chronic pain experienced by over 50 million people in the United States, and may come with substantial adverse effects signifying the need to find novel treatments. One novel therapeutic target is the Transient Receptor Potential A1 channel (TRPA1), an ion channel that mediates nociception through calcium influx of sensory neurons. Drug discovery still relies heavily on animal models, including zebrafish, a species in which TRPA1 activation produces hyperlocomotion. Here, we investigated if this hyperlocomotion follows zebrafish TRPA1 pharmacology and evaluated the strengths and limitations of using TRPA1-mediated hyperlocomotion as potential preclinical screening tool for drug discovery. To support face validity of the model, we pharmacologically characterized mouse and zebrafish TRPA1 in transfected HEK293 cells using calcium assays as well as in vivo. TRPA1 agonists and antagonists respectively activated or blocked TRPA1 activity in HEK293 cells, mice, and zebrafish in a dose-dependent manner. However, our results revealed complexities including partial agonist activity of TRPA1 antagonists, bidirectional locomotor activity, receptor desensitization, and off-target effec...Continue Reading

References

Feb 3, 2005·Nature Reviews. Drug Discovery·Leonard I Zon, Randall T Peterson
Mar 3, 2005·The Journal of Biological Chemistry·Vladislav BugajGalina N Mozhayeva
Aug 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Diana M BautistaPeter M Zygmunt
Jan 16, 2007·Handbook of Experimental Pharmacology·M Tominaga
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Colleen R McNamaraChristopher M Fanger
Nov 21, 2007·Trends in Pharmacological Sciences·David Colquhoun
Dec 19, 2007·Molecular Pain·Matt PetrusArdem Patapoutian
Oct 3, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David A ProberAlexander F Schier
Apr 30, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Robert Gerlai
Jun 10, 2011·American Journal of Physiology. Cell Physiology·Manish RaisinghaniLouis S Premkumar
Aug 2, 2011·Nature Reviews. Drug Discovery·Magdalene M MoranArpad Szallasi
Sep 6, 2011·Biological Psychiatry·Richard M van RijnJennifer L Whistler
Oct 26, 2012·The Journal of Pharmacology and Experimental Therapeutics·Richard M van RijnJennifer L Whistler
Jan 26, 2013·Molecular Medicine·Veronica Gonzalez-NunezRaquel E Rodríguez
Apr 18, 2013·Zebrafish·Allan V KalueffUNKNOWN Zebrafish Neuroscience Research Consortium
Dec 3, 2013·European Journal of Pharmacology·Ryosuke KojimaHiroyuki Itou
Mar 29, 2014·Reviews of Physiology, Biochemistry and Pharmacology·Romina NassiniPierangelo Geppetti
Feb 3, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Jun Chen, David H Hackos
Dec 15, 2015·Nature Methods·Shijia ChenDavid A Prober
Mar 18, 2016·MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports·Deborah DowellRoger Chou
Mar 16, 2017·Physiology & Behavior·J Christopher TaylorRobert E Sorge
Jun 3, 2017·International Journal of Molecular Sciences·Logan GanzenMingzhi Zhang
Oct 20, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joey S StevensAimen K Farraj

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Citations

Jun 17, 2020·Frontiers in Neuroscience·Abdul-Azim HassanChris David Keating
Oct 28, 2020·The Journal of Experimental Biology·William A HaneyJames A Strother
Apr 27, 2021·Frontiers in Neuroscience·Nils OhnesorgeLars Lewejohann

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