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

GPCR Desensitization01:12

GPCR Desensitization

5.6K
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...
5.6K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

10.9K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
10.9K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.8K
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...
1.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.1K
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...
5.1K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

1.8K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
1.8K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

6.5K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.5K

You might also read

Related Articles

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

Sort by
Same author

The gut microbial lauroyl tryptamine antagonizes oxysterol-GPR183 signaling to modulate lipid-sensitive metabolic pathways in a sex-dependent manner.

Biochimica et biophysica acta. Molecular and cell biology of lipids·2026
Same author

Multicolored sequential resonance energy transfer for detection of simultaneous ligand binding at G protein-coupled receptors.

Nature communications·2025
Same author

Allosteric modulation and biased signalling at free fatty acid receptor 2.

Nature·2025
Same author

Chronic administration of hydrolysed pine nut oil to mice improves insulin sensitivity and glucose tolerance and increases energy expenditure via a free fatty acid receptor 4-dependent mechanism.

The British journal of nutrition·2024
Same author

Drug Repurposing in Crohn's Disease Using Danish Real-World Data.

Pragmatic and observational research·2024
Same author

Structure-Activity Relationship Studies and Optimization of 4-Hydroxypyridones as GPR84 Agonists.

Journal of medicinal chemistry·2024

Related Experiment Video

Updated: May 16, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.8K

Minimal Structural Variation of GPR84 Full Agonist Causes Functional Switch to Inverse Agonism.

Loukas Ieremias1, Asmita Manandhar1, Katrine Schultz-Knudsen1

  • 1Department of Drug Design and Pharmacology, Faculty of Health, University of Copenhagen, 2100 Copenhagen Ø, Denmark.

Journal of Medicinal Chemistry
|April 4, 2025
PubMed
Summary

Researchers discovered that a small structural change can turn GPR84 agonists into inverse agonists. This led to the development of potent GPR84 inverse agonists and antagonists for treating inflammatory diseases.

More Related Videos

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

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

18.3K
Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

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

Published on: June 9, 2017

16.2K

Related Experiment Videos

Last Updated: May 16, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.8K
Quantifying Agonist Activity at G Protein-coupled Receptors
11:45

Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

18.3K
Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

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

Published on: June 9, 2017

16.2K

Area of Science:

  • Pharmacology
  • Immunology
  • Medicinal Chemistry

Background:

  • G protein-coupled receptor 84 (GPR84) is primarily expressed in immune cells like neutrophils and macrophages.
  • GPR84 plays a role in modulating immune responses during inflammation.
  • GPR84 is a promising drug target for inflammatory and fibrotic disorders.

Purpose of the Study:

  • To discover novel GPR84 modulators by exploring structure-activity relationships.
  • To identify compounds that can switch GPR84 activity from agonism to inverse agonism or antagonism.
  • To develop potent and selective GPR84 inhibitors for potential therapeutic applications.

Main Methods:

  • Systematic structural modifications of GPR84 ligands.
  • Structure-activity relationship (SAR) studies.
  • In vitro assays to assess GPR84 functional activity, selectivity, and neutrophil activation.

Main Results:

  • A minor structural modification successfully switched GPR84 agonists into inverse agonists.
  • Identification of low-nanomolar potency inverse agonists and antagonists, including TUG-2181 (40g).
  • Compounds demonstrated favorable physicochemical properties, selectivity against other free fatty acid receptors, and effective inhibition of GPR84-mediated neutrophil activation.

Conclusions:

  • GPR84 inverse agonists and antagonists can be effectively developed through targeted structural modifications.
  • The identified compounds, such as TUG-2181, show potential as therapeutic agents for inflammatory and fibrotic conditions.
  • These findings support GPR84 as a viable target for drug development in inflammatory diseases.