Related Experiment Video
Updated: Jul 16, 2026
14:26
In vivo Quantification of G Protein Coupled Receptor Interactions using Spectrally Resolved Two-photon Microscopy
Published on: January 19, 2011
[The quantitative patterns of the modified one-center bioreceptor model]
1N. N. Semenov Institute of Chemical Physics, Russian Academy of Science, Moscow, Russia. poltorakov@mtu-net.ru
Zhurnal Obshchei Biologii
|June 23, 2000
Summary
A modified one-site model quantitatively estimates full agonism, determining threshold phenomena and spare receptors. This model accurately fits dose-response curves for full agonists, aiding in receptor analysis.
Area of Science:
- Pharmacology and Computational Biology
- Biochemistry and Biophysics
Background:
- Understanding full agonism is crucial for drug development and receptor theory.
- Existing models may not fully capture the quantitative aspects of agonist-receptor interactions.
Purpose of the Study:
- To quantitatively estimate the phenomenon of full agonism using a modified one-site bioreceptor model.
- To determine threshold phenomena, spare receptors, and the linear dependence of biological effect on agonist-receptor complex concentration.
Main Methods:
- Utilized a modified one-site model for bioreceptor analysis.
- Developed general correlation equations to describe the dose-response relationship.
- Applied the model to experimental dose-response curves.
Main Results:
- The one-site model equations provided a good fit to experimental dose-response curves for full agonists.
- Successfully calculated the value of spare receptors.
- Demonstrated the model's ability to determine threshold phenomena and linear dependence.
Conclusions:
- The modified one-site model offers a quantitative approach to understanding full agonism.
- The model accurately predicts spare receptors and dose-response relationships.
- This framework is applicable to analyzing interactions like acetylcholine with muscarinic receptors.
Related Concept Videos
01:30Transducer Mechanism: G Protein–Coupled Receptors
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, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...
01:30Spare Receptors
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
01:30Quantitative 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...
01:29The 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...
The binding affinity of a drug determines its interaction with one...
01:23Mechanistic Models: Compartment Models in Individual and Population Analysis
Mechanistic models are utilized in individual analysis using single-source data, but imperfections arise due to data collection errors, preventing perfect prediction of observed data. The mathematical equation involves known values (Xi), observed concentrations (Ci), measurement errors (εi), model parameters (ϕj), and the related function (ƒi) for i number of values. Different least-squares metrics quantify differences between predicted and observed values. The ordinary least squares (OLS)...
01:29Pharmacodynamic Models: Direct Effect Model and Indirect Response Model
Pharmacodynamic models are essential tools in understanding the relationship between drug concentrations and their effects on biological systems. By characterizing the dynamics of drug action, these models guide dose selection, optimize therapeutic efficacy, and inform the development of new drugs. Two major classes of pharmacodynamic models include direct effect and indirect response models.Direct Effect ModelsDirect effect models describe the immediate relationship between drug concentration...