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Cellular tolerance at the µ-opioid receptor is phosphorylation dependent
Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-termi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873894/ https://www.ncbi.nlm.nih.gov/pubmed/29589831 http://dx.doi.org/10.7554/eLife.34989 |
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author | Arttamangkul, Seksiri Heinz, Daniel A Bunzow, James R Song, Xianqiang Williams, John T |
author_facet | Arttamangkul, Seksiri Heinz, Daniel A Bunzow, James R Song, Xianqiang Williams, John T |
author_sort | Arttamangkul, Seksiri |
collection | PubMed |
description | Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus coeruleus neurons in a MOR knockout rat. Both receptors activated potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, acutely desensitized, internalized and, after chronic morphine treatment, displayed signs of tolerance. However, TPD receptors did not desensitize or internalize with agonist treatment. In addition the TPD receptors did not develop cellular tolerance following chronic morphine treatment. Thus C-terminal phosphorylation is necessary for the expression of acute desensitization, trafficking and one sign of long-term tolerance to morphine at the cellular level. |
format | Online Article Text |
id | pubmed-5873894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-58738942018-03-29 Cellular tolerance at the µ-opioid receptor is phosphorylation dependent Arttamangkul, Seksiri Heinz, Daniel A Bunzow, James R Song, Xianqiang Williams, John T eLife Neuroscience Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus coeruleus neurons in a MOR knockout rat. Both receptors activated potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, acutely desensitized, internalized and, after chronic morphine treatment, displayed signs of tolerance. However, TPD receptors did not desensitize or internalize with agonist treatment. In addition the TPD receptors did not develop cellular tolerance following chronic morphine treatment. Thus C-terminal phosphorylation is necessary for the expression of acute desensitization, trafficking and one sign of long-term tolerance to morphine at the cellular level. eLife Sciences Publications, Ltd 2018-03-28 /pmc/articles/PMC5873894/ /pubmed/29589831 http://dx.doi.org/10.7554/eLife.34989 Text en © 2018, Arttamangkul et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Arttamangkul, Seksiri Heinz, Daniel A Bunzow, James R Song, Xianqiang Williams, John T Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title | Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title_full | Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title_fullStr | Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title_full_unstemmed | Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title_short | Cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
title_sort | cellular tolerance at the µ-opioid receptor is phosphorylation dependent |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873894/ https://www.ncbi.nlm.nih.gov/pubmed/29589831 http://dx.doi.org/10.7554/eLife.34989 |
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