Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system

Authors

  • X Rovira,

    1. Grup Biomatemàtic de Recerca, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain, and
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    • *

      Authors contributed equally to this work.

  • M Vivó,

    1. School of Pharmacy, University of Reading, Reading, Berkshire, UK
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    • 3

      Present address: Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.

    • *

      Authors contributed equally to this work.

  • J Serra,

    1. Grup Biomatemàtic de Recerca, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain, and
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  • D Roche,

    1. Grup Biomatemàtic de Recerca, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain, and
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  • PG Strange,

    1. School of Pharmacy, University of Reading, Reading, Berkshire, UK
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  • J Giraldo

    1. Grup Biomatemàtic de Recerca, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain, and
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Dr J Giraldo, Grup Biomatemàtic de Recerca, Institut de Neurociències and Unitat de Bioestadística, Facultat de Medicina, Universiat Autònoma de Barcelona, Spain. E-mail: Jesus.Giraldo@uab.es

Abstract

Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

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