Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

2.6K
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,...
2.6K
GPCR Desensitization01:12

GPCR Desensitization

6.9K
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...
6.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

6.6K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.6K
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.7K
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...
2.7K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

3.2K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

6.2K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Phosphorylation site topology governs the functional dynamics of arrestin recruitment to GPCRs.

Research square·2026
Same author

Robust functional ultrasound imaging in the awake and behaving brain: A systematic framework for motion artifact removal.

Imaging neuroscience (Cambridge, Mass.)·2026
Same author

Opioid-specific brain connectivity dynamics distinguish analgesia from secondary effects: Studies in male mice.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Cell-based and isoform-selective G protein-coupled receptor kinase assays for comprehensive inhibitor evaluation.

Communications biology·2026
Same author

Somatostatin receptor subtypes 1 and 4 regulate neprilysin, the major amyloid-β degrading enzyme in brain.

Journal of Alzheimer's disease : JAD·2025
Same author

Helix-bundle and C-terminal GPCR domains differentially influence GRK-specific functions and β-arrestin-mediated regulation.

Nature communications·2025

Related Experiment Video

Updated: Oct 25, 2025

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

11.7K

SR-17018 Stimulates Atypical µ-Opioid Receptor Phosphorylation and Dephosphorylation.

Sebastian Fritzwanker1, Stefan Schulz1, Andrea Kliewer1

  • 1Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Straße 1, D-07747 Jena, Germany.

Molecules (Basel, Switzerland)
|August 7, 2021
PubMed
Summary
This summary is machine-generated.

New research reveals that SR-17018, a biased µ-opioid receptor (MOP) agonist, causes unique, long-lasting MOP phosphorylation. This finding offers novel insights into opioid pharmacology and potential therapeutic strategies for opioid-associated risks.

Keywords:
DAMGOSR-17018buprenorphineµ-opioid receptor

More Related Videos

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
07:48

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

Published on: July 3, 2015

9.0K
Quantifying Agonist Activity at G Protein-coupled Receptors
11:45

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

19.4K

Related Experiment Videos

Last Updated: Oct 25, 2025

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

11.7K
Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
07:48

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

Published on: July 3, 2015

9.0K
Quantifying Agonist Activity at G Protein-coupled Receptors
11:45

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

19.4K

Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • Opioid-associated overdoses and deaths are a significant public health concern.
  • G-protein-biased µ-opioid receptor (MOP) agonists are being developed to mitigate opioid risks.
  • SR-17018 was initially identified as a biased MOP agonist with a wide therapeutic window.

Purpose of the Study:

  • To investigate the temporal dynamics of SR-17018-induced MOP phosphorylation and dephosphorylation.
  • To compare SR-17018's MOP phosphorylation profile with other MOP agonists.
  • To explore the potential pharmacological implications of distinct MOP phosphorylation patterns.

Main Methods:

  • Exposure of MOP to saturating concentrations of SR-17018 and DAMGO.
  • Analysis of MOP phosphorylation and dephosphorylation kinetics after agonist washout.
  • Inclusion of naloxone during washout to assess reversibility.

Main Results:

  • SR-17018 induced a MOP phosphorylation pattern similar to DAMGO but with significantly delayed dephosphorylation.
  • SR-17018-induced MOP phosphorylation persisted for hours, unlike the rapid reversal seen with DAMGO.
  • Reversibility of SR-17018-induced phosphorylation was dependent on naloxone presence.

Conclusions:

  • SR-17018 exhibits unique temporal MOP phosphorylation kinetics compared to other MOP agonists.
  • Detailed analysis of MOP phosphorylation dynamics can reveal unappreciated pharmacological properties of novel ligands.
  • This research may inform the development of safer opioid-based therapeutics.