Related Experiment Video
Updated: Jan 16, 2026
10:13
Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
17.1K
Membrane disruption attenuates agonist potency in prostanoid receptors
Uurtuya Hochban1, Imke Wallenstein1, Michaela Ulrich1
1Department of Pharmacy, Marburg University, Institute of Pharmacology and Clinical Pharmacy, Marburg, Germany.
The Biochemical Journal
|September 29, 2025
Summary
Membrane integrity significantly impacts G protein-coupled receptor (GPCR) function, affecting ligand binding affinity. This finding is crucial for accurate drug discovery and structural studies of these important signaling proteins.
Area of Science:
- Biochemistry
- Pharmacology
- Molecular Biology
Background:
- G protein-coupled receptors (GPCRs) are crucial drug targets, but their function is often studied in disrupted membrane environments.
- The impact of membrane integrity on GPCR function and ligand binding has not been systematically investigated.
Purpose of the Study:
- To investigate the effect of membrane integrity on GPCR conformation and ligand binding affinity.
- To develop and utilize Förster resonance energy transfer (FRET)-based sensors for real-time GPCR activation measurements.
Main Methods:
- Development of FRET-based GPCR conformation sensors.
- Measurement of GPCR activation in both intact and disrupted cell membranes.
- Validation using wildtype receptors in functional signaling assays.
Main Results:
- GPCRs exhibit varying dependence on membrane integrity; prostanoid receptors showed up to 30-fold decrease in ligand potency upon membrane disruption.
- This indicates a critical role of membrane integrity in determining ligand-receptor affinity.
- Effects were confirmed to reflect genuine receptor characteristics, not sensor artifacts.
Conclusions:
- Membrane integrity is a critical factor influencing GPCR ligand binding affinity and function.
- Experimental conditions must account for membrane integrity to avoid bias in structural and pharmacological studies.
- Optimized experimental strategies are essential for reliable GPCR data interpretation.
Related Concept Videos
01:12GPCR Desensitization
7.9K
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...
7.9K
01:25Drug-Receptor Interaction: Agonist
4.0K
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...
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
4.0K
01:28Drug-Receptor Interaction: Antagonist
4.9K
An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
Antagonists can be classified as competitive or noncompetitive based on their...
4.9K
01:29Drug-Receptor Interactions
7.3K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
7.3K
01:22Opioid Receptors: Overview
4.1K
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,...
4.1K
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
1.1K
The gastric mucosa produces prostaglandins E2 (PGE2) and prostacyclin (PGI2), crucial in maintaining gastric health. They exert cytoprotective effects, including increasing bicarbonate secretion, releasing protective mucin, reducing gastric acid output, and preventing harmful vasoconstriction. These effects are mediated through various receptors, such as EP1, EP2, EP3, and EP4.
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
1.1K