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Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons
Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly us...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346451/ https://www.ncbi.nlm.nih.gov/pubmed/18461159 http://dx.doi.org/10.1371/journal.pone.0002082 |
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author | Stotz, Stephanie C. Vriens, Joris Martyn, Derek Clardy, Jon Clapham, David E. |
author_facet | Stotz, Stephanie C. Vriens, Joris Martyn, Derek Clardy, Jon Clapham, David E. |
author_sort | Stotz, Stephanie C. |
collection | PubMed |
description | Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. |
format | Text |
id | pubmed-2346451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-23464512008-05-07 Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons Stotz, Stephanie C. Vriens, Joris Martyn, Derek Clardy, Jon Clapham, David E. PLoS One Research Article Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. Public Library of Science 2008-05-07 /pmc/articles/PMC2346451/ /pubmed/18461159 http://dx.doi.org/10.1371/journal.pone.0002082 Text en Stotz et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Stotz, Stephanie C. Vriens, Joris Martyn, Derek Clardy, Jon Clapham, David E. Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title | Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title_full | Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title_fullStr | Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title_full_unstemmed | Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title_short | Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons |
title_sort | citral sensing by transient receptor potential channels in dorsal root ganglion neurons |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346451/ https://www.ncbi.nlm.nih.gov/pubmed/18461159 http://dx.doi.org/10.1371/journal.pone.0002082 |
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