title: Selective activation of hTRPV1 by N-geranyl cyclopropylcarboxamide, an amiloride-insensitive salt taste enhancer.
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 Ca(2+)-flux signaling assay in cultured cells. NGCC enhanced Ca(2+) influx in hTRPV1-expressing cells in a dose-dependent manner (EC50 = 115 µM). NGCC-induced Ca(2+) 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 Ca(2+) influx in hTRPA1-expressing cells (EC50 = 83.65 µM). The NGCC-induced Ca(2+) 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.
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Son
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Yiseul
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Brain Science, DaeguGyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Kweon
authors.affiliation: Department of Brain Science, DaeguGyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.
authors.forename: Byung-Chang
authors.initials: BC
authors.lastname: Suh
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
authors.affiliation: Division of Metabolism and Functionality Research, Korea Food Research Institute, Bundang-gu, Sungnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Mee-Ra
authors.initials: MR
authors.lastname: Rhyu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000577:Amides / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology*; D015220:Calcium Channels / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D039821:Monoterpenes / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013650:Taste Buds / Q000187:drug effects / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects*; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000235:genetics
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D000577:Amides; D015220:Calcium Channels; D053503:Epithelial Sodium Channels; D039821:Monoterpenes; C582720:N-geranyl cyclopropylcarboxamide; D009419:Nerve Tissue Proteins; D017673:Sodium Chloride, Dietary; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; D000584:Amiloride