scholarly journals An Emerging Role for the Delta Opioid Receptor in the Regulation of Mu Opioid Receptor Function

2007 ◽  
Vol 7 ◽  
pp. 64-73 ◽  
Author(s):  
Raphael Rozenfeld ◽  
Noura S. Abul-Husn ◽  
Ivone Gomez ◽  
Lakshmi A. Devi
Keyword(s):  
Opioid Receptor ◽  
Critical Role ◽  
Site Occupancy ◽  
Morphine Tolerance ◽  
Delta Opioid Receptor ◽  
Receptor Binding Site ◽  
Delta Opioid Receptors ◽  
Physiological Adaptations ◽  
Opiate Tolerance ◽  
The Impact

Morphine and related opiates are commonly used in the clinical management of various types of pain. However, the antinociceptive properties of morphine are often overshadowed by the development of tolerance and dependence following its chronic use. The mechanisms underlying opiate tolerance are not fully understood, but appear to involve numerous and complex physiological adaptations. Recently, a role for the heterodimerization of mu and delta opioid receptors in the development of morphine tolerance has been proposed. This novel mechanism could help us to understand several observations, such as the critical role of delta opioid receptor regulation, the impact of delta opioid receptor binding site occupancy, and the participation of beta-arrestin2, in the development of morphine tolerance.

scholarly journals Behavioral Consequences of Delta-Opioid Receptor Activation in the Periaqueductal Gray of Morphine Tolerant Rats

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Michael M. Morgan ◽  
Michelle D. Ashley ◽  
Susan L. Ingram ◽  
MacDonald J. Christie
Keyword(s):  
Plasma Membrane ◽  
Morphine Tolerance ◽  
Receptor Activation ◽  
Delta Opioid Receptor ◽  
Morphine Injection ◽  
Chronic Morphine ◽  
Delta Opioid Receptors ◽  
Morphine Administration ◽  
Consistent Manner ◽  
Deltorphin Ii

Chronic morphine administration shifts delta-opioid receptors (DORs) from the cytoplasm to the plasma membrane. Given that microinjection of morphine into the PAG produces antinociception, it is hypothesized that the movement of DORs to the membrane will allow antinociception to the DOR agonist deltorphin II as a way to compensate for morphine tolerance. Tolerance was induced by twice daily injections of morphine (5, 10, or 20 mg/kg, subcutaneous) for 3.5 days. Microinjection of deltorphin into the vPAG 6 hours after the last morphine injection produced a mild antinociception that did not vary in a consistent manner across morphine pretreatment doses or nociceptive tests. In contrast, deltorphin caused a decrease in activity in morphine tolerant rats that was associated with lying in the cage. The decrease in activity and change in behavior indicate that chronic morphine administration alters DORs in the vPAG. However, activation of these receptors does not appear to compensate for the decrease in antinociception caused by morphine tolerance.

scholarly journals Heteromerization of Endogenous Mu and Delta Opioid Receptors Induces Ligand-Selective Co-Targeting to Lysosomes

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4493 ◽  
Author(s):  
Lyes Derouiche ◽  
Florian Pierre ◽  
Stéphane Doridot ◽  
Stéphane Ory ◽  
Dominique Massotte
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Acid Ethyl Ester ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Therapeutic Drugs ◽  
Delta Opioid Receptors ◽  
The Impact ◽  
Fine Tune ◽  
Intracellular Fate

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. We established ligand selective mu–delta co-internalization upon activation by 1-[[4-(acetylamino)phenyl]methyl]-4-(2-phenylethyl)-4-piperidinecarboxylic acid, ethyl ester (CYM51010), [d-Ala2, NMe-Phe4, Gly-ol5]enkephalin (DAMGO), and deltorphin II, but not (+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80), morphine, or methadone. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors, and led to sorting to the lysosomal compartment. Altogether, our data indicate that mu–delta co-expression, likely through heteromerization, alters the intracellular fate of the mu opioid receptor, which provides a way to fine-tune mu opioid receptor signaling. It also represents an interesting emerging concept for the development of novel therapeutic drugs and strategies.

scholarly journals Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity

2013 ◽  
Vol 23 (19) ◽  
pp. 5267-5269 ◽  
Author(s):  
Arnaud Proteau-Gagné ◽  
Kristina Rochon ◽  
Mélissa Roy ◽  
Pierre-Julien Albert ◽  
Brigitte Guérin ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Activity ◽  
Delta Opioid Receptor ◽  
The Impact

Mo1873 The Impact of Internalization on Compartmentalized Signaling of the Delta Opioid Receptor

2015 ◽  
Vol 148 (4) ◽  
pp. S-732
Author(s):  
Lih En Tiah ◽  
Nigel W. Bunnett ◽  
Pradeep Rajasekhar ◽  
Holly Yeatman ◽  
Daniel P. Poole ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Delta Opioid Receptor ◽  
The Impact

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

2018 ◽  
Author(s):  
Lyes Derouiche ◽  
Muzeyyen Ugur ◽  
Florian Pierre ◽  
Anika Mann ◽  
Stéphane Doridot ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Mu Opioid Receptor ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Mu Opioid ◽  
Nociceptive Transmission ◽  
Delta Opioid Receptors ◽  
The Impact

AbstractIncreasing 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 co-internalization upon activation by exogenous ligands and provide evidence for mu-delta co-internalization by the endogenous opioid peptide met-enkephalin, but not β-endorphin. Co-internalization 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

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

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