Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Dec;115(6):1363-81.
doi: 10.1097/ALN.0b013e318238bba6.

Molecular mechanisms of opioid receptor-dependent signaling and behavior

Ream Al-Hasani  1 , Michael R Bruchas
Affiliations
Review

Molecular mechanisms of opioid receptor-dependent signaling and behavior

Ream Al-Hasani et al. Anesthesiology. 2011 Dec.

Abstract

Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibitory G proteins. These receptors form homo- and heterodimeric complexes and signal to kinase cascades and scaffold a variety of proteins.The authors discuss classic mechanisms and developments in understanding opioid tolerance and opioid receptor signaling and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. The authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, the authors conclude there is a continued need for more translational work on opioid receptors in vivo.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Sites of action of opioid analgesics
The grey pathway shows the sites of action on the pain transmission pathway from periphery to central nervous system. The red pathway shows the actions on pain modulating neurons in the mid brain and medulla. Abrevations: MOR- μ opioid receptor
Figure 2
Figure 2. Summary of Opioid Receptor Signaling
Cartoon depicting opioid receptor signal transduction and trafficking. In general, all four opioid receptor subtypes, μ, δ, κ, and ORL1 share these common pathways. New research indicates that selective-ligands at each opioid receptor can direct opioid receptors to favor one or more of these signaling events (biased agonism, or ligand directed signaling). Arrows refer to activation steps; T lines refer to blockade or inhibition of function. Abbreviations: α G-protein alphai subunit, arrestin phosphorylation- dependent GPCR scaffold, βγ- G-protein beta-gamma subunit, cAMP- cyclic adenosine monophosphate, ERK ½ - extra-cellular signal- regulated kinase, JNK - c-Jun N-terminal kinase, p38- p38 MAPK, P- phosphorylation
Figure 3
Figure 3. Opioid Dimerization
A cartoon depicting (A) Opioid receptor homodimers and opioid receptor heterodimers (B) Heterodimers between opioid receptors and other G-Protein coupled receptors (C) Protein-protein interactions involved in opioid receptor signal transduction. Abbreviations: βγ- G-protein beta-gamma subunit, μ- μ opioid receptor, δ- δ opioid receptor, CB1- Cannabinoid receptor type 1, κ- κ opioid receptor, ORL-1- opioid receptor like-1
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M. International Union of Pharmacology. XII: Classification of receptors. Pharmacol. Rev. 1996;48:567–592. - PubMed
    1. Bruchas MR, Chavkin C. Kinase cascades and ligand-directed signaling at the kappa opioid receptor. Psychopharmacology (Berl.) 2010;210:137–147. - PMC - PubMed
    1. Walwyn WM, Miotto KA, Evans CJ. Opioid pharmaceuticals and addiction: The issues and research directions seeking solutions. Drug Alcohol Depend. 2010;108:156–165. - PMC - PubMed
    1. Ahlbeck K. Opioids: A two-faced Janus. Curr Med Res Opin. 2011;27:439–448. - PubMed
    1. McNicol E, Horowicz-Mehler N, Fisk RA, Bennett K, Gialeli-Goudas M, Chew PW, Lau J, Carr D. Management of opioid side effects in cancer-related and chronic noncancer pain: A systematic review. J Pain. 2003;4:231–256. - PubMed

Publication types