Nicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel

Awani Upadhyay, Aditya Pisupati, Timothy Jegla, Matt Crook, Keith J. Mickolajczyk, Matthew Shorey, Laura E. Rohan, Katherine A. Billings, Melissa M. Rolls, William O. Hancock, Wendy Hanna-Rose

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Abstract

TRPV ion channels are directly activated by sensory stimuli and participate in thermo-, mechano- and chemo-sensation. They are also hypothesized to respond to endogenous agonists that would modulate sensory responses. Here, we show that the nicotinamide (NAM) form of vitamin B3 is an agonist of a Caenorhabditis elegans TRPV channel. Using heterologous expression in Xenopus oocytes, we demonstrate that NAM is a soluble agonist for a channel consisting of the well-studied OSM-9 TRPV subunit and relatively uncharacterized OCR-4 TRPV subunit as well as the orthologous Drosophila Nan-Iav TRPV channel, and we examine stoichiometry of subunit assembly. Finally, we show that behaviours mediated by these C. elegans and Drosophila channels are responsive to NAM, suggesting conservation of activity of this soluble endogenous metabolite on TRPV activity. Our results in combination with the role of NAM in NAD+ metabolism suggest an intriguing link between metabolic regulation and TRPV channel activity.

Original languageEnglish (US)
Article number13135
JournalNature communications
Volume7
DOIs
StatePublished - Oct 12 2016

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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