Abstract
Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating multiple splice variants or isoforms via a variety of alternative splicing events. These OPRM1 splice variants can be categorized into three major types based on the receptor structure: (1) full-length 7 transmembrane (TM) C-terminal variants; (2) truncated 6TM variants; and (3) single TM variants. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating the distinct actions of various mu opioids. More importantly, the OPRM1 variants can be targeted for development of novel opioid analgesics that are potent against multiple types of pain, but devoid of many side-effects associated with traditional opiates. In this review, we provide an overview of OPRM1 alternative splicing and its functional relevance in opioid pharmacology.
Highlights
Published: 15 October 2021The actions of most clinically used opioid analgesics, such as morphine and fentanyl, are complex
The concept of multiple mu opioid receptors was originally suggested based on clinical observations that different patients displayed divergent responses to mu opioids in analgesia, and in side-effects and that incomplete cross-tolerance among mu opioids led to the clinical practice of opioid rotation
Unlike mMOR-1K that is associated with exon 11, hMOR-1K did not have exon 11 and its expression appeared to be controlled by its own promoter located at upstream of the human exon 13
Summary
The actions of most clinically used opioid analgesics, such as morphine and fentanyl, are complex They provide potent analgesia, they produce many undesirable side-effects such as respiratory depression, constipation, pruritus, physical dependence, and addiction. Patients often showed divergent responses to mu opioids in analgesia and in side-effects, and incomplete cross-tolerance among mu opioids led to the clinical practice of opioid rotation These observations suggest the presence of multiple mu opioid receptors, a concept that was originally proposed by early pharmacological studies [8,9,10] and evolved by recent molecular studies of the mu opioid receptor gene, OPRM1 [11,12]. This review outlines the progress regarding OPRM1 alternative splicing and its pharmacological functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
