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Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats
Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755923/ https://www.ncbi.nlm.nih.gov/pubmed/29304162 http://dx.doi.org/10.1371/journal.pone.0191032 |
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author | Matsushita, Yumi Manabe, Miki Kitamura, Naoki Shibuya, Izumi |
author_facet | Matsushita, Yumi Manabe, Miki Kitamura, Naoki Shibuya, Izumi |
author_sort | Matsushita, Yumi |
collection | PubMed |
description | Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at –60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α(2) antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α(2) agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5’- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α(2)-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway. |
format | Online Article Text |
id | pubmed-5755923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57559232018-01-26 Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats Matsushita, Yumi Manabe, Miki Kitamura, Naoki Shibuya, Izumi PLoS One Research Article Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at –60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α(2) antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α(2) agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5’- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α(2)-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway. Public Library of Science 2018-01-05 /pmc/articles/PMC5755923/ /pubmed/29304162 http://dx.doi.org/10.1371/journal.pone.0191032 Text en © 2018 Matsushita 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Matsushita, Yumi Manabe, Miki Kitamura, Naoki Shibuya, Izumi Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title | Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title_full | Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title_fullStr | Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title_full_unstemmed | Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title_short | Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats |
title_sort | adrenergic receptors inhibit trpv1 activity in the dorsal root ganglion neurons of rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755923/ https://www.ncbi.nlm.nih.gov/pubmed/29304162 http://dx.doi.org/10.1371/journal.pone.0191032 |
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