Related Experiment Video

Updated: Aug 8, 2026

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors
10:59

Use of Label-free Optical Biosensors to Detect Modulation of Potassium Channels by G-protein Coupled Receptors

Published on: February 11, 2014

mu-Opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization

Veronica A Alvarez1, Seksiri Arttamangkul, Vu Dang

  • 1Vollum Institute and Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon 97201, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|July 5, 2002
PubMed

Insights

Opioid receptor desensitization and internalization are linked, but agonist properties, not just efficacy, determine their efficiency. Understanding these biophysical properties is key to better opioid signaling insights.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Cell Biology

Background:

  • Micro-opioid receptor (MOR) desensitization and endocytosis are linked to opioid tolerance and dependence.
  • Agonist-dependent efficiency of these processes is known, but the determining factors remain unclear.

Purpose of the Study:

  • To investigate the relative efficiency of various agonists in causing MOR desensitization and endocytosis.
  • To determine the relationship between MOR desensitization in neurons and internalization in cell lines.

Main Methods:

  • Examined homologous MOR desensitization in locus ceruleus (LC) neurons using various agonists.
  • Assessed MOR internalization in HEK293 cells with the same series of agonists.
  • Compared agonist rank orders for hyperpolarization, desensitization, and endocytosis.

Main Results:

  • Agonist rank orders differed for hyperpolarization versus desensitization in LC neurons.
  • The ability of agonists to cause MOR endocytosis in HEK293 cells strongly correlated with their ability to desensitize MOR in LC neurons.
  • Agonist efficacy did not reliably predict the capacity for MOR desensitization or endocytosis.

Conclusions:

  • MOR desensitization and endocytosis are closely linked processes.
  • Biophysical properties of agonists, beyond mere efficacy, dictate their ability to induce MOR desensitization and internalization.
  • Characterizing these properties will advance understanding of opioid signaling and potentially inform the development of safer analgesics.

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

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding10:13

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding

Published on: June 9, 2017

Related Concept Videos

Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
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...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
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, D-Pen5]-enkephalin or DPDPE for...
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...
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...