Abstract
The description of the allosteric modification of receptors to affect changes in their function requires a model that considers the effects of the modulator on both agonist affinity and efficacy. A model is presented which describes changes in affinity in terms of the constant α (ratio of affinity in the presence vs the absence of modulator) and also the constant ξ (ratio of intrinsic efficacy of the agonist in the presence vs absence of modulator). This allows independent effects of both affinity and efficacy and allows the modeling of any change in the dose-response curve to an agonist after treatment with modulator. Examples are given where this type of model can predict effects of modulators that reduce efficacy but actually increase affinity of agonist (i.e. ifenprodil) and also of modulators that block the action of some agonists (the CXCR4 agonist SDF-1α by the antagonist AMD3100) but not others for the same receptor (SDF-1α peptide fragments RSVM and ASLW).
Keywords: allosteric effects, radioligand binding assay, NMDA receptor, HIV entry, CXCR4, Probe
Current Neuropharmacology
Title: Allosteric Theory: Taking Therapeutic Advantage of the Malleable Nature of GPCRs
Volume: 5 Issue: 3
Author(s): Terry Kenakin
Affiliation:
Keywords: allosteric effects, radioligand binding assay, NMDA receptor, HIV entry, CXCR4, Probe
Abstract: The description of the allosteric modification of receptors to affect changes in their function requires a model that considers the effects of the modulator on both agonist affinity and efficacy. A model is presented which describes changes in affinity in terms of the constant α (ratio of affinity in the presence vs the absence of modulator) and also the constant ξ (ratio of intrinsic efficacy of the agonist in the presence vs absence of modulator). This allows independent effects of both affinity and efficacy and allows the modeling of any change in the dose-response curve to an agonist after treatment with modulator. Examples are given where this type of model can predict effects of modulators that reduce efficacy but actually increase affinity of agonist (i.e. ifenprodil) and also of modulators that block the action of some agonists (the CXCR4 agonist SDF-1α by the antagonist AMD3100) but not others for the same receptor (SDF-1α peptide fragments RSVM and ASLW).
Export Options
About this article
Cite this article as:
Kenakin Terry, Allosteric Theory: Taking Therapeutic Advantage of the Malleable Nature of GPCRs, Current Neuropharmacology 2007; 5 (3) . https://dx.doi.org/10.2174/157015907781695973
DOI https://dx.doi.org/10.2174/157015907781695973 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Endothelial Dysfunction in Morbid Obesity
Current Pharmaceutical Design Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms
CNS & Neurological Disorders - Drug Targets Myalgic Encephalomyelitis: Symptoms and Biomarkers
Current Neuropharmacology Targeting Opioid and Neurokinin-1 Receptors to Treat Alcoholism
Current Medicinal Chemistry Prenatal Stress Enhances Susceptibility to Allergic Diseases of Offspring
Endocrine, Metabolic & Immune Disorders - Drug Targets Effects of Thiazolidinediones Beyond Glycaemic Control
Current Pharmaceutical Design Protein Trafficking and Alzheimers Disease
Current Alzheimer Research Amantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness
Current Pharmaceutical Design Editorial [Hot Topic: Novel Therapeutic Strategies in Neural Diseases Uncover Unexpected Disease Connections: From Neurodegeneration and Addiction to Pain and Depression (Guest Editor: Gonzalo Herradon)]
Current Pharmaceutical Design Interactions of Sex Steroids with Mechanisms of Inflammation
Current Drug Targets - Inflammation & Allergy Cannabis and Psychosis: A Systematic Review of Genetic Studies
Current Psychiatry Reviews PLGA Nanoparticles and Polysorbate-80-Coated PLGA Nanoparticles Increase the In vitro Antioxidant Activity of Melatonin
Current Drug Delivery Hyperhomocysteinaemia: A Critical Review of Old and New Aspects
Current Drug Metabolism Molecular Biology of the Enzymes that Degrade Endocannabinoids
Current Drug Targets - CNS & Neurological Disorders Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?
Current Genomics Psychiatric Side Effects of Interferon Treatment
Current Drug Safety Recent Patents Pertaining to Immune Modulation and Musculoskeletal Regeneration with Wharton’s Jelly Cells
Recent Patents on Regenerative Medicine Bioactive Peptides from Marine Organisms: A Short Overview
Protein & Peptide Letters Melatonin and Synthetic Analogs as Antioxidants
Current Drug Delivery Patent Selections:
Recent Patents on Drug Delivery & Formulation