Related Experiment Video

Updated: Jun 17, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
09:09

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

Published on: September 20, 2016

Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene

Michael A Ansonoff1, Ting Wen, John E Pintar

  • 1Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.

Frontiers in Bioscience (Scholar Edition)
|December 29, 2009
PubMed

Insights

Knocking out the DOR-1 gene alters kappa opioid receptor expression and enhances analgesia. This suggests the DOR-1 gene is crucial for kappa2 opioid receptor function and potentially KOR-1/DOR-1 heterodimer activity.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Opioid receptors are known to form homo- and heterodimers in cell lines.
  • The in vivo relevance of these receptor interactions remains incompletely understood.

Purpose of the Study:

  • To investigate the in vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors following the knockout of specific opioid receptor genes.
  • To determine the role of the DOR-1 gene in the expression and function of kappa opioid receptor subtypes.

Main Methods:

  • Utilized opioid receptor knockout mice, specifically targeting the DOR-1 gene.
  • Employed radioligand binding assays using diprenorphine to assess receptor density in crude membrane preparations.
  • Conducted cumulative dose-response curves with the kappa opioid agonist U69,593 to evaluate analgesic potency.

Main Results:

  • Knockout or occupancy of the DOR-1 gene led to an increased binding density of kappa1 receptors.
  • The DOR-1 gene knockout resulted in the elimination of kappa2 receptors, while total kappa opioid binding sites remained unchanged.
  • Analgesic potency of U69,593 was significantly enhanced in mice lacking the DOR-1 gene.

Conclusions:

  • The DOR-1 gene is essential for the in vivo expression of the kappa2 opioid receptor subtype.
  • These findings support the hypothesis that a kappa opioid receptor 1 (KOR-1)/delta opioid receptor 1 (DOR-1) heterodimer may mediate kappa2 opioid receptor pharmacology.
  • The study highlights the importance of receptor heterodimerization in modulating opioid receptor function and analgesia.

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

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...
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...
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 one...
Drug-Receptor Interaction: Agonist01:25

Drug-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.
Quantitative Aspects of Drug-Receptor Interaction01:30

Quantitative Aspects of Drug-Receptor Interaction

The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower Kd...