Selective Activation of hTRPV1 by N-Geranyl Cyclopropylcarboxamide, an Amiloride-Insensitive Salt Taste Enhancer

Authors

Min Jung Kim, Korea Food Research Institute
Hee Jin Son, Korea Food Research Institute
Yiseul Kim, Korea Food Research Institute
Hae-Jin Kweon, DaeguGyeongbuk Institute of Science and Technology
Byung-Chang Suh, DaeguGyeongbuk Institute of Science and Technology
Vijay Lyall, Virginia Commonwealth UniversityFollow
Mee-Ra Rhyu, Korea Food Research Institute

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

PLOS ONE

Volume

9

DOI of Original Publication

10.1371/journal.pone.0089062

Comments

Originally Published at http://dx.doi.org/10.1371/journal.pone.0089062

Date of Submission

November 2014

Abstract

TRPV1t, a variant of the transient receptor potential vanilloid-1 (TRPV1) has been proposed as a constitutively active, non-selective cation channel as a putative amiloride-insensitive salt taste receptor and shares many properties with TRPV1. Based on our previous chorda tympani taste nerve recordings in rodents and human sensory evaluations, we proposed that N-geranylcyclopropylcarboxamide (NGCC), a novel synthetic compound, acts as a salt taste enhancer by modulating the amiloride/benzamil-insensitive Na+ entry pathways. As an extension of this work, we investigated NGCC-induced human TRPV1 (hTRPV1) activation using a Ca2+-flux signaling assay in cultured cells. NGCC enhanced Ca2+ influx in hTRPV1-expressing cells in a dose-dependent manner (EC50 = 115 µM). NGCC-induced Ca2+ influx was significantly attenuated by ruthenium red (RR; 30 µM), a non-specific blocker of TRP channels and capsazepine (CZP; 5 µM), a specific antagonist of TRPV1, implying that NGCC directly activates hTRPV1. TRPA1 is often co-expressed with TRPV1 in sensory neurons. Therefore, we also investigated the effects of NGCC on hTRPA1-expressing cells. Similar to hTRPV1, NGCC enhanced Ca2+ influx in hTRPA1-expressing cells (EC50 = 83.65 µM). The NGCC-induced Ca2+ influx in hTRPA1-expressing cells was blocked by RR (30 µM) and HC-030031 (100 µM), a specific antagonist of TRPA1. These results suggested that NGCC selectively activates TRPV1 and TRPA1 in cultured cells. These data may provide additional support for our previous hypothesis that NGCC interacts with TRPV1 variant cation channel, a putative amiloride/benzamil-insensitive salt taste pathway in the anterior taste receptive field.

Rights

© 2014 Kim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Physiology and Biophysics Publications