Related Experiment Video

Updated: Apr 11, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
16:02

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation

Published on: February 10, 2023

3.5K

A new splice of life for the μ-opioid receptor

Michael J Iadarola, Matthew R Sapio, Andrew J Mannes

    The Journal of Clinical Investigation
    |May 27, 2015
    PubMed

    Insights

    A novel 6 transmembrane (6TM) opioid receptor isoform provides pain relief in mice. This 6TM receptor is distinct from the standard 7 transmembrane (7TM) receptor and may offer a safer alternative for pain management.

    Area of Science:

    • Neuroscience
    • Pharmacology
    • Molecular Biology

    Background:

    • μ-Opioid agonists are key analgesics, acting via G protein-coupled receptors (GPCRs) from the Oprm1 transcript.
    • Most μ-opioids interact with the canonical 7 transmembrane (7TM) receptor.
    • A newly identified class of μ-opioids may utilize a 6 transmembrane (6TM) receptor variant.

    Purpose of the Study:

    • To demonstrate in vivo proof-of-concept for a 6TM μ-opioid receptor isoform supporting functional analgesia.
    • To characterize the pharmacological properties and therapeutic potential of the 6TM isoform.

    Main Methods:

    • In vivo studies using Oprm1-deficient animals.
    • Pharmacological characterization of the 6TM vs. 7TM μ-opioid receptor isoforms.
    • Assessment of analgesic efficacy and side effect profiles.

    Main Results:

    • The 6TM μ-opioid receptor isoform successfully mediated functional analgesia in vivo.
    • The 6TM isoform exhibited distinct pharmacological properties compared to the canonical 7TM receptor.
    • Agonists targeting the 6TM isoform demonstrated a reduced side effect profile.

    Conclusions:

    • A 6TM μ-opioid receptor isoform can mediate analgesia, offering a potential therapeutic advantage.
    • This discovery opens new avenues for analgesic drug discovery by expanding opioid-receptor neurobiology and pharmacology.
    • The 6TM receptor represents a promising target for developing safer and more effective pain management strategies.

    More Related Videos

    Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis07:48

    Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis

    Published on: July 3, 2015

    9.3K
    Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography09:09

    Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography

    Published on: September 20, 2016

    12.1K

    Related Concept Videos

    Opioid Receptors: Overview01:22

    Opioid Receptors: Overview

    Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
    6.9K
    Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

    Opioid Analgesics: Synthetic and Semisynthetic Opioids

    Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
    1.5K
    Opioid Analgesics: Morphine and Other Natural Cogeners01:20

    Opioid Analgesics: Morphine and Other Natural Cogeners

    Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
    1.6K
    Analgesia and Pain Management01:25

    Analgesia and Pain Management

    Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
    3.1K
    The Two-State Receptor Model01:29

    The Two-State Receptor Model

    The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
    The binding affinity of a drug determines its interaction with...
    3.6K
    GPCR Desensitization01:12

    GPCR Desensitization

    G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
    8.8K