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PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons
Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696243/ https://www.ncbi.nlm.nih.gov/pubmed/29190977 http://dx.doi.org/10.18632/oncotarget.21805 |
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author | Wu, Jing Wang, Jia-Jia Liu, Ting-Ting Zhou, Yi-Mei Qiu, Chun-Yu Shen, Ding-Wen Hu, Wang-Ping |
author_facet | Wu, Jing Wang, Jia-Jia Liu, Ting-Ting Zhou, Yi-Mei Qiu, Chun-Yu Shen, Ding-Wen Hu, Wang-Ping |
author_sort | Wu, Jing |
collection | PubMed |
description | Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-α antagonist. Moreover, PPAR-α activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats. These results indicated that activation of peripheral PPAR-α acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-α. |
format | Online Article Text |
id | pubmed-5696243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56962432017-11-29 PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons Wu, Jing Wang, Jia-Jia Liu, Ting-Ting Zhou, Yi-Mei Qiu, Chun-Yu Shen, Ding-Wen Hu, Wang-Ping Oncotarget Research Paper Peroxisome proliferator-activated receptor-α (PPAR-α), a lipid activated transcription factor of nuclear hormone receptor superfamily, can relieve pain through a rapid-response mechanism. However, little is known about the underlying mechanism. Herein, we report that PPAR-α activation acutely inhibits the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglion (DRG) neurons. Pre-application of PPAR-α agonist GW7647 for 2 min decreased the amplitude of proton-gated currents mediated by ASICs in a concentration-dependent manner. GW7647 shifted the concentration-response curve for proton downwards, with a decrease of 36.9 ± 2.3% in the maximal current response to proton. GW7647 inhibition of proton-gated currents can be blocked by GW6471, a selective PPAR-α antagonist. Moreover, PPAR-α activation decreased the number of acidosis-evoked action potentials in rat DRG neurons. Finally, peripheral administration of GW7647 dose-dependently relieved nociceptive responses to injection of acetic acid in rats. These results indicated that activation of peripheral PPAR-α acutely inhibited functional activity of ASICs in a non-genomic manner, which revealed a novel mechanism underlying rapid analgesia through peripheral PPAR-α. Impact Journals LLC 2017-10-10 /pmc/articles/PMC5696243/ /pubmed/29190977 http://dx.doi.org/10.18632/oncotarget.21805 Text en Copyright: © 2017 Wu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Wu, Jing Wang, Jia-Jia Liu, Ting-Ting Zhou, Yi-Mei Qiu, Chun-Yu Shen, Ding-Wen Hu, Wang-Ping PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title | PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title_full | PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title_fullStr | PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title_full_unstemmed | PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title_short | PPAR-α acutely inhibits functional activity of ASICs in rat dorsal root ganglion neurons |
title_sort | ppar-α acutely inhibits functional activity of asics in rat dorsal root ganglion neurons |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696243/ https://www.ncbi.nlm.nih.gov/pubmed/29190977 http://dx.doi.org/10.18632/oncotarget.21805 |
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