Functional relevance of μ–δ opioid receptor heteromerization: A Role in novel signaling and implications for the treatment of addiction disorders: From a symposium on new concepts in mu-opioid pharmacology

Abstract

Morphine and other opiates are among the most widely prescribed and clinically useful medications for the treatment of chronic pain. However, the applicability of these compounds has been severely hampered by the rapid development of tolerance and physical dependence that typically accompanies their repeated use. A growing body of evidence has implicated the regulated functioning of μ-δ opioid receptor heteromers in both the modulation of morphine-mediated antinociception, and in the limitation of undesirable side effects resulting from chronic opiate exposure. Moreover, μ-δ heteromers exhibit unique ligand binding characteristics and signaling properties, indicating that pharmacological targeting of the μ-δ heteromer may represent a novel therapeutic approach for the management of chronic pain and addiction disorders. Therefore, the present review will attempt to summarize the latest relevant findings regarding the regulation and functional characteristics of the μ-δ heteromer both in vitro and in vivo.

15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse

“…Also, as many other systems, this receptor contributes to chronic morphine-induced neuroplasticity. Mechanisms underlying a potential cross talk between delta receptor activity and mu opioid receptor signaling in vivo remain unclear (see (Pradhan et al, 2011; Stockton and Devi, 2012). …”

Pharmacogenetics of OPRM1

“…Activation of MOR or DOR results in rewarding effects and analgesia, while KOR is involved in aversion and dysphoria. Opioid receptor heterodimers also occur in vivo and have been shown to regulate unique phenotypes that differ from those regulated by the individual receptor types, adding further complexity to opioid receptor signaling (reviewed in [2]).…”

Regulation ofµ-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance

“…Similar approaches have not yet been applied to the MOR so stability of oligomers remains uncertain. A number of reviews on opioid receptor oligomers summarize this evolving area and it will not be discussed further here (Agnati et al, 2003;Smith and Milligan, 2010;Costantino et al, 2012;Stockton and Devi, 2012). …”