Prolonged morphine treatment alters δ opioid receptor post‐internalization trafficking

Ong, Edmund; Xue, Ling; Olmstead, Mary C.; Cahill, Catherine M.

doi:10.1111/bph.12761

Cited by 20 publications

(13 citation statements)

References 72 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Receptor subtypes may be differentially trafficked following internalization. For example, DORs may be degraded after trafficking to lysosomes, whereas MORs are recycled to the cell surface (Ong et al ., ). However, specific details of opioid receptor trafficking in cardiomyocytes are lacking.…”

Section: Opioid and Opioid Receptor Expression In The Heartmentioning

confidence: 97%

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Headrick

Hoe

Toit

et al. 2015

British J Pharmacology

135

View full text Add to dashboard Cite

Ischaemic heart disease (IHD) remains a major cause of morbidity/mortality globally, firmly established in Westernized or 'developed' countries and rising in prevalence in developing nations. Thus, cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, is a very important, although still elusive, clinical goal. The opioid receptor system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) opioid receptors and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears as a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central opioid receptor signalling may also enhance the ability of the heart to withstand I-R injury. The δ-and κ-opioid receptors are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ opioid receptor-dependent protection in animal and human tissues. A small number of clinical trials have provided evidence of cardiac benefit from morphine or remifentanil in cardiopulmonary bypass or coronary angioplasty patients, although further trials of subtype-specific opioid receptor agonists are needed. The precise roles and utility of this GPCR family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on opioid receptor signalling and protective responses.

show abstract

Section: Opioid and Opioid Receptor Expression In The Heartmentioning

confidence: 97%

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Headrick

Hoe

Toit

et al. 2015

British J Pharmacology

135

View full text Add to dashboard Cite

show abstract

“…Culture dorsal root ganglia neurons from adult animals as described 12 . Use adult-neuron growth medium to culture the cells.…”

Section: Cell Culturementioning

confidence: 99%

“…Scale bars show 10 µm. Adapted from 12 under the provisions of CC BY-NC 3.0. Please click here to view a larger version of this figure.…”

Section: Drug Treatment Of Cultured Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis

Ong

Cahill

2015

JoVE

View full text Add to dashboard Cite

The intracellular trafficking of receptors is a collection of complex and highly controlled processes. Receptor trafficking modulates signaling and overall cell responsiveness to ligands and is, itself, influenced by intra-and extracellular conditions, including ligand-induced signaling. Optimized for use with monolayer-plated cultured cells, but extendable to free-floating tissue slices, this protocol uses immunolabelling and colocalizational analysis to track changes in intracellular receptor trafficking following both chronic/prolonged and acute interventions, including exogenous drug treatment. After drug treatment, cells are double-immunolabelled for the receptor and for markers for the intracellular compartments of interest. Sequential confocal microscopy is then used to capture two-channel photomicrographs of individual cells, which are subjected to computerized colocalizational analysis to yield quantitative colocalization scores. These scores are normalized to permit pooling of independent replicates prior to statistical analysis. Representative photomicrographs may also be processed to generate illustrative figures. Here, we describe a powerful and flexible technique for quantitatively assessing induced receptor trafficking. Video LinkThe video component of this article can be found at

show abstract

“…In addition, constitutive recruitment of βarrestin 2 by mu-delta heteromers was observed in SKNSH neuroblastoma cells that affected ERK1/2 signaling ). Finally, the mu agonist DAMGO induced cointernalization and co-recycling of mu and delta opioid receptors in DRG cultures pretreated with morphine, suggesting that mu-delta heteromerization may affect the trafficking of the delta opioid receptor in these conditions (Ong et al 2015). However, further work is now needed to fully apprehend functional changes induced by mu-delta heteromerization, in particular upon activation by endogenous opioid peptides.…”

Section: Introductionmentioning

confidence: 99%

Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking

Derouiche¹,

Ugur²,

Pierre³

et al. 2018

Preprint

View full text Add to dashboard Cite

Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures and in vivo. We established ligand selective mu-delta cointernalization upon activation by exogenous ligands and provide evidence for mu-delta cointernalization by the endogenous opioid peptide met-enkephalin, but not β-endorphin. Cointernalization was driven by the delta opioid receptor, required an active conformation of both receptors and led to sorting to the lysosomal compartment. This alteration in the mu opioid receptor intracellular fate was accompanied by sustained ERK1/2 phosphorylation. In addition, increased mu-delta neuronal co-localization in the rostral ventromedial medulla in a chronic neuropathic state suggests that mu-delta heteromers are involved in the regulation of nociceptive transmission Keywords G protein-coupled receptors, opioid receptor, heteromers, internalization, ERK phosphorylation, neuropathic pain, fluorescent knock-in mice, endogenous opioid peptides, hippocampus, rostral ventromedial medulla

show abstract

Prolonged morphine treatment alters δ opioid receptor post‐internalization trafficking

Cited by 20 publications

References 72 publications

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis

Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking

Contact Info

Product

Resources

About