Prolonged morphine treatment alters δ opioid receptor post-internalization trafficking
Autor: | Edmund Ong, Mary C. Olmstead, Lihua Xue, Catherine M. Cahill |
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Rok vydání: | 2013 |
Předmět: |
Agonist
Male medicine.medical_specialty SDM-25N medicine.drug_class media_common.quotation_subject Receptors Opioid mu deltorphin II Pharmacology Naltrexone Piperazines Rats Sprague-Dawley chemistry.chemical_compound Opioid receptor trafficking Internal medicine Ganglia Spinal Receptors Opioid delta medicine Functional selectivity Animals δ opioid receptor Receptor Internalization Cells Cultured media_common Mice Knockout Neurons Themed Section: Opioids: New Pathways to Functional Selectivity Morphine μ opioid receptor Chemistry DAMGO dorsal root ganglia Enkephalin Ala(2)-MePhe(4)-Gly(5) Receptor antagonist Analgesics Opioid internalization Protein Transport Endocrinology SNC80 Benzamides Oligopeptides medicine.drug Research Paper |
Zdroj: | British Journal of Pharmacology |
ISSN: | 1476-5381 |
Popis: | © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. Background and Purpose The δ opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. Experimental Approach Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. Key Results A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The μ opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. Conclusions and Implications The results support the hypothesis that prolonged morphine treatment induces the formation of MOP-DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. |
Databáze: | OpenAIRE |
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