Desensitized D2 autoreceptors are resistant to trafficking

Abstract Dendritic release of dopamine activates dopamine D2 autoreceptors, which are inhibitory G protein-coupled receptors (GPCRs), to decrease the excitability of dopamine neurons. This study used tagged D2 receptors to identify the localization and distribution of these receptors in living midbr...

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Autores principales: Brooks G. Robinson, James R. Bunzow, Jonathan B. Grimm, Luke D. Lavis, Joshua T. Dudman, Jennifer Brown, Kim A. Neve, John T. Williams
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/cd52b855e0284c209df9fce0fd4cbae8
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spelling oai:doaj.org-article:cd52b855e0284c209df9fce0fd4cbae82021-12-02T11:40:58ZDesensitized D2 autoreceptors are resistant to trafficking10.1038/s41598-017-04728-z2045-2322https://doaj.org/article/cd52b855e0284c209df9fce0fd4cbae82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04728-zhttps://doaj.org/toc/2045-2322Abstract Dendritic release of dopamine activates dopamine D2 autoreceptors, which are inhibitory G protein-coupled receptors (GPCRs), to decrease the excitability of dopamine neurons. This study used tagged D2 receptors to identify the localization and distribution of these receptors in living midbrain dopamine neurons. GFP-tagged D2 receptors were found to be unevenly clustered on the soma and dendrites of dopamine neurons within the substantia nigra pars compacta (SNc). Physiological signaling and desensitization of the tagged receptors were not different from wild type receptors. Unexpectedly, upon desensitization the tagged D2 receptors were not internalized. When tagged D2 receptors were expressed in locus coeruleus neurons, a desensitizing protocol induced significant internalization. Likewise, when tagged µ-opioid receptors were expressed in dopamine neurons they too were internalized. The distribution and lack of agonist-induced internalization of D2 receptors on dopamine neurons indicate a purposefully regulated localization of these receptors.Brooks G. RobinsonJames R. BunzowJonathan B. GrimmLuke D. LavisJoshua T. DudmanJennifer BrownKim A. NeveJohn T. WilliamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Brooks G. Robinson
James R. Bunzow
Jonathan B. Grimm
Luke D. Lavis
Joshua T. Dudman
Jennifer Brown
Kim A. Neve
John T. Williams
Desensitized D2 autoreceptors are resistant to trafficking
description Abstract Dendritic release of dopamine activates dopamine D2 autoreceptors, which are inhibitory G protein-coupled receptors (GPCRs), to decrease the excitability of dopamine neurons. This study used tagged D2 receptors to identify the localization and distribution of these receptors in living midbrain dopamine neurons. GFP-tagged D2 receptors were found to be unevenly clustered on the soma and dendrites of dopamine neurons within the substantia nigra pars compacta (SNc). Physiological signaling and desensitization of the tagged receptors were not different from wild type receptors. Unexpectedly, upon desensitization the tagged D2 receptors were not internalized. When tagged D2 receptors were expressed in locus coeruleus neurons, a desensitizing protocol induced significant internalization. Likewise, when tagged µ-opioid receptors were expressed in dopamine neurons they too were internalized. The distribution and lack of agonist-induced internalization of D2 receptors on dopamine neurons indicate a purposefully regulated localization of these receptors.
format article
author Brooks G. Robinson
James R. Bunzow
Jonathan B. Grimm
Luke D. Lavis
Joshua T. Dudman
Jennifer Brown
Kim A. Neve
John T. Williams
author_facet Brooks G. Robinson
James R. Bunzow
Jonathan B. Grimm
Luke D. Lavis
Joshua T. Dudman
Jennifer Brown
Kim A. Neve
John T. Williams
author_sort Brooks G. Robinson
title Desensitized D2 autoreceptors are resistant to trafficking
title_short Desensitized D2 autoreceptors are resistant to trafficking
title_full Desensitized D2 autoreceptors are resistant to trafficking
title_fullStr Desensitized D2 autoreceptors are resistant to trafficking
title_full_unstemmed Desensitized D2 autoreceptors are resistant to trafficking
title_sort desensitized d2 autoreceptors are resistant to trafficking
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/cd52b855e0284c209df9fce0fd4cbae8
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