| Nerve growth factor-regulated emergence of functional delta-opioid receptors. | |
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MedLine Citation:
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PMID: 20410114 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sorting of intracellular G-protein-coupled receptors (GPCRs) either to lysosomes for degradation or to plasma membrane for surface insertion and functional expression is a key process regulating signaling strength of GPCRs across the plasma membrane in adult mammalian cells. However, little is known about the molecular mechanisms governing the dynamic process of receptor sorting to the plasma membrane for functional expression under normal and pathological conditions. In this study, we demonstrate that delta-opioid receptor (DOPr), a GPCR constitutively targeted to intracellular compartments, is driven to the surface membrane of central synaptic terminals and becomes functional by the neurotrophin nerve growth factor (NGF) in native brainstem neurons. The NGF-triggered DOPr translocation is predominantly mediated by the signaling pathway involving the tyrosine receptor kinase A, Ca(2+)-mobilizing phospholipase C, and Ca(2+)/calmodulin-dependent protein kinase II. Importantly, it requires interactions with the cytoplasmic sorting protein NHERF-1 (Na(+)/H(+) exchange regulatory factor-1) and N-ethyl-maleimide-sensitive factor-regulated exocytosis. In addition, this NGF-mediated mechanism is likely responsible for the emergence of functional DOPr induced by chronic opioids. Thus, NGF may function as a key molecular switch that redirects the sorting of intracellularly targeted DOPr to plasma membrane, resulting in new functional DOPr on central synapses under chronic opioid conditions. |
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Authors:
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Bihua Bie; Zhi Zhang; You-Qing Cai; Wei Zhu; Yong Zhang; Jaile Dai; Charles J Lowenstein; Edward J Weinman; Zhizhong Z Pan |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 30 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-22 Completed Date: 2010-05-04 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 5617-28 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, The University of Texas-MD Anderson Cancer Center, Houston, Texas 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Excitatory Postsynaptic Potentials / drug effects, physiology Male Mice Mice, Knockout Morphine / pharmacology Nerve Growth Factor / pharmacology*, physiology* Rats Rats, Wistar Receptors, Opioid, delta / agonists, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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DA023069/DA/NIDA NIH HHS; DA025826/DA/NIDA NIH HHS; R01 DA023069-02/DA/NIDA NIH HHS; R01 DA027541-01/DA/NIDA NIH HHS; R21 DA025826-02/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Opioid, delta; 57-27-2/Morphine; 9061-61-4/Nerve Growth Factor |
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