Molecular mechanisms of opioid receptor-dependent signaling and behavior
- PMID: 22020140
- PMCID: PMC3698859
- DOI: 10.1097/ALN.0b013e318238bba6
Molecular mechanisms of opioid receptor-dependent signaling and behavior
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.
Figures



Similar articles
-
Pharmacological mechanisms of opioid analgesics.Clin Neuropharmacol. 1993 Feb;16(1):1-18. doi: 10.1097/00002826-199302000-00001. Clin Neuropharmacol. 1993. PMID: 8093680 Review.
-
Mu Receptors.2024 Jun 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. 2024 Jun 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 31855381 Free Books & Documents.
-
Opioids.Handb Exp Pharmacol. 2007;(177):31-63. doi: 10.1007/978-3-540-33823-9_2. Handb Exp Pharmacol. 2007. PMID: 17087119 Review.
-
RGS proteins: new players in the field of opioid signaling and tolerance mechanisms.Anesth Analg. 2005 Apr;100(4):1034-1042. doi: 10.1213/01.ANE.0000147711.51122.4B. Anesth Analg. 2005. PMID: 15781518
-
Activity of the delta-opioid receptor is partially reduced, whereas activity of the kappa-receptor is maintained in mice lacking the mu-receptor.J Neurosci. 1998 Sep 15;18(18):7285-95. doi: 10.1523/JNEUROSCI.18-18-07285.1998. J Neurosci. 1998. PMID: 9736649 Free PMC article.
Cited by
-
Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.Methods Mol Biol. 2021;2201:139-162. doi: 10.1007/978-1-0716-0884-5_13. Methods Mol Biol. 2021. PMID: 32975796 Free PMC article. Review.
-
Finding the Perfect Fit: Conformational Biosensors to Determine the Efficacy of GPCR Ligands.ACS Pharmacol Transl Sci. 2022 Aug 14;5(9):694-709. doi: 10.1021/acsptsci.1c00256. eCollection 2022 Sep 9. ACS Pharmacol Transl Sci. 2022. PMID: 36110374 Free PMC article. Review.
-
Spinal microglial β-endorphin signaling mediates IL-10 and exenatide-induced inhibition of synaptic plasticity in neuropathic pain.CNS Neurosci Ther. 2021 Oct;27(10):1157-1172. doi: 10.1111/cns.13694. Epub 2021 Jun 10. CNS Neurosci Ther. 2021. PMID: 34111331 Free PMC article.
-
Toll-Like Receptor 4 (TLR4)/Opioid Receptor Pathway Crosstalk and Impact on Opioid Analgesia, Immune Function, and Gastrointestinal Motility.Front Immunol. 2020 Jul 8;11:1455. doi: 10.3389/fimmu.2020.01455. eCollection 2020. Front Immunol. 2020. PMID: 32733481 Free PMC article. Review.
-
"I'll Be Back": The Resurrection of Dezocine.ACS Med Chem Lett. 2021 May 19;12(6):961-968. doi: 10.1021/acsmedchemlett.1c00233. eCollection 2021 Jun 10. ACS Med Chem Lett. 2021. PMID: 34141081 Free PMC article.
References
-
- 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
-
- Ahlbeck K. Opioids: A two-faced Janus. Curr Med Res Opin. 2011;27:439–448. - PubMed
-
- 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
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials