Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Targets for Drug Action: Overview

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

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:

Amplifying Signals via Enzymatic Cascade

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...

Ligand-Gated Ion Channel Receptor: Gating Mechanism

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...

G Protein-coupled Receptors

G Protein-coupled Receptors

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...

GPCR Desensitization

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...

You might also read

Related Articles

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

Sort by

Same author

DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence.

ACS pharmacology & translational science·2023

Same author

Aging-related modifications to G protein-coupled receptor signaling diversity.

Pharmacology & therapeutics·2020

Same author

Reply to Schierwagen et al.: β-Arrestins in liver disease.

Proceedings of the National Academy of Sciences of the United States of America·2020

Same author

SnapShot: β-Arrestin Functions.

Cell·2020

Same author

β-Arrestin2 is a critical component of the GPCR-eNOS signalosome.

Proceedings of the National Academy of Sciences of the United States of America·2020

Same author

Conformational Sensors and Domain Swapping Reveal Structural and Functional Differences between β-Arrestin Isoforms.

Cell reports·2019

Search research articles

Related Experiment Video

Updated: May 10, 2026

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

Arrestin pathways as drug targets.

Louis M Luttrell¹

¹Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Progress in Molecular Biology and Translational Science

|June 15, 2013

Summary

This summary is machine-generated.

Biased agonists selectively target G protein-coupled receptor (GPCR) pathways, offering therapeutic potential. However, in vitro efficacy does not reliably predict in vivo effects, necessitating a new framework for drug discovery.

More Related Videos

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Related Experiment Videos

Last Updated: May 10, 2026

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Area of Science:

Pharmacology
Molecular Biology
Drug Discovery

Background:

G protein-coupled receptors (GPCRs) exhibit complex efficacy profiles.
Ligand bias allows selective modulation of GPCR signaling pathways.
Arrestins are key non-G protein effectors of GPCRs.

Purpose of the Study:

To explore the concept of biased agonism at GPCRs.
To investigate the disconnect between in vitro and in vivo effects of biased ligands.
To propose a framework for predicting in vivo actions of biased agonists.

Main Methods:

Review of existing literature on GPCR efficacy and biased agonism.
Analysis of in vitro and in vivo data for arrestin-biased ligands.
Conceptual development of a predictive framework.

Main Results:

Biased agonists activate specific GPCR signaling subsets in vitro.
In vivo effects of biased ligands can unpredictably diverge from in vitro profiles.
Arrestin-mediated signaling plays a crucial role in these divergent effects.

Conclusions:

A deeper understanding of GPCR pluridimensionality is essential for drug development.
Current in vitro assays may not fully capture the in vivo complexity of biased ligands.
A rational framework is needed to bridge in vitro and in vivo findings for successful biased ligand drug discovery.