Cellular Signalling of Non-synonymous Single-nucleotide Polymorphisms of the Human μ-opioid Receptor (OPRM1)

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2014 Feb 18

PMID 24527749

Citations 13

Authors

Alisa Knapman

Mark Connor

Affiliations

Soon will be listed here.

Abstract

Unlabelled: There is significant variability in individual responses to opioid drugs, which is likely to have a significant genetic component. A number of non-synonymous single-nucleotide polymorphisms (SNPs) in the coding regions of the μ-opioid receptor gene (OPRM1) have been postulated to contribute to this variability. Although many studies have investigated the clinical influences of these μ-opioid receptor variants, the outcomes are reported in the context of thousands of other genes and environmental factors, and we are no closer to being able to predict individual response to opioids based on genotype. Investigation of how μ-opioid receptor SNPs affect their expression, coupling to second messengers, desensitization and regulation is necessary to understand how subtle changes in receptor structure can impact individual responses to opioids. To date, the few functional studies that have investigated the consequences of SNPs on the signalling profile of the μ-opioid receptor in vitro have shown that the common N40D variant has altered functional responses to some opioids, while other, rarer, variants display altered signalling or agonist-dependent regulation. Here, we review the data available on the effects of μ-opioid receptor polymorphisms on receptor function, expression and regulation in vitro, and discuss the limitations of the studies to date. Whether or not μ-opioid receptor SNPs contribute to individual variability in opioid responses remains an open question, in large part because we have relatively little good data about how the amino acid changes affect μ-opioid receptor function.

Linked Articles: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Citing Articles

Functional differences in the mu opioid receptor SNP 118A>G are dependent on receptor splice-variant and agonist-specific recruitment of β-arrestin.

Patrick C, Ettah U, Nguyen V, Hart C, Atchley E, Mallela K Clin Transl Sci. 2024; 17(8):e13888.

PMID: 39118392 PMC: 11310404. DOI: 10.1111/cts.13888.

Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone.

Manandhar P, Connor M, Santiago M Pharmacol Res Perspect. 2022; 10(1):e00921.

PMID: 35084120 PMC: 8929351. DOI: 10.1002/prp2.921.

The μ-opioid receptor gene A118G polymorphism is associated with insecure attachment in children with disruptive mood regulation disorder and their mothers.

Cimino S, Carola V, Cerniglia L, Bussone S, Bevilacqua A, Tambelli R Brain Behav. 2020; 10(7):e01659.

PMID: 32424914 PMC: 7375094. DOI: 10.1002/brb3.1659.

Serotonin 5-HT Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.

Land M, Chapman H, Davis-Reyes B, Felsing D, Allen J, Moeller F Sci Rep. 2019; 9(1):16737.

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Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits.

Li J, Wei Z, Zhang J, Hakonarson H, Cook-Sather S Pharmacogenomics J. 2019; 19(6):570-581.

PMID: 30760877 PMC: 6693985. DOI: 10.1038/s41397-019-0074-4.

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