Related Experiment Video
Updated: May 10, 2026
07:48
Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
Published on: July 3, 2015
Novel Ligands for the Orphan Receptor GPR151 Modulate Morphine Action
Hijiri Yoshida1, Takashi Suto2, Hiroyuki Hirano3
1Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma, Japan.
Summary
Researchers identified novel G protein-coupled receptor 151 (GPR151) ligands, GUM3 and GUM4, that modulate pain pathways. These compounds show potential for developing new pain management strategies and reducing opioid dependence.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- G protein-coupled receptor 151 (GPR151) is expressed on specific neurons.
- Upregulation of GPR151 in dorsal root ganglia suggests a role in pain transmission.
Purpose of the Study:
- To identify novel agonists and partial agonists for GPR151.
- To investigate the role of GPR151 in pain pathways.
- To explore GPR151 as a potential drug target for pain control.
Main Methods:
- Utilized a unique ligand screening system to discover GPR151 ligands.
- Assessed ligand activity using [35S]-GTPγS binding assays.
- Evaluated ligand-induced GPR151 internalization and reporter gene expression.
- Examined the effects of ligands on thermal hyperalgesia and morphine analgesia in rats.
Main Results:
- Identified novel GPR151 agonists (GUM3) and partial agonists (GUM4) with psoralen ring structures.
- GUM3 and GUM4 induced GPR151 internalization and reporter gene expression.
- Co-administration of GPR151 ligands modulated morphine's analgesic effects, with the agonist enhancing and the partial agonist attenuating it.
Conclusions:
- GPR151 plays a physiological role in pain transmission.
- GPR151 is a promising novel drug target for pain management.
- Development of GPR151 ligands may aid in reducing opioid use.
More Related Videos
Related Concept Videos
01:22Opioid 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...
01:25Analgesia 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...
01:15Opioid 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...
01:20Opioid 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...
01:25Drug-Receptor Interaction: Agonist
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
01:30Ligand-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...