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Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene, OPRM1: Insight into Complex Mu Opioid Actions

Shan Liu1, Wen-Jia Kang1, Anna Abrimian1

  • 1Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.

Biomolecules
|October 23, 2021
PubMed

Insights

Mu opioid receptor (OPRM1) gene splicing creates variants impacting opioid drug actions. Targeting these OPRM1 variants offers potential for developing effective pain relievers with fewer side effects.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Genetics

Background:

  • Mu opioid receptor (MOR) is a key target for opioid analgesics like morphine and fentanyl.
  • The MOR gene (OPRM1) exhibits extensive alternative splicing, producing diverse receptor variants.
  • These OPRM1 variants differ in structure, including full-length, truncated 6TM, and single TM forms.

Purpose of the Study:

  • To review the alternative splicing of the OPRM1 gene.
  • To discuss the functional relevance of OPRM1 splice variants in opioid pharmacology.
  • To highlight the therapeutic potential of OPRM1 variants for novel pain management strategies.

Main Methods:

  • Literature review of OPRM1 alternative splicing.
  • Analysis of structural classifications of OPRM1 variants.
  • Examination of pharmacological evidence for OPRM1 variant functions.

Main Results:

  • OPRM1 gene undergoes extensive alternative splicing, generating multiple functional isoforms.
  • OPRM1 splice variants exhibit distinct pharmacological properties.
  • Evidence suggests OPRM1 variants mediate differential effects of various mu opioids.

Conclusions:

  • OPRM1 splice variants are crucial in determining opioid efficacy and side effect profiles.
  • Targeting specific OPRM1 variants could lead to the development of safer and more potent analgesics.
  • Understanding OPRM1 splicing is vital for advancing opioid-based pain therapeutics.
Keywords:
GPCROPRM1alternative splicingbiased signalingfentanylgene targetingmorphinemu opioid receptoropioidpain

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