Agonist induction, conformational selection, and mutant receptors

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13 Citations (Scopus)

Abstract

Current models of receptor activation are based on either of two basic mechanisms: agonist induction or conformational selection. The importance of one pathway relative to the other is controversial. In this article, the impossibility of distinguishing between the two mechanisms under a thermodynamic approach is shown. The effect of receptor mutation on the constants governing ligand-receptor equilibria is discussed. The two-state model of agonism both in its original formulation (one cycle) and including multiple active states (multiple cycles) is used. Pharmacological equations for the double (two cycles) two-state model are derived. The simulations performed suggest that the double two-state model of agonism can be a useful model for assessing quantitatively the changes in pharmacological activity following receptor mutation. © 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)13-18
JournalFEBS Letters
Volume556
DOIs
Publication statusPublished - 2 Jan 2004

Keywords

  • Agonist induction
  • Conformational selection
  • G protein-coupled receptor
  • Multiple state
  • Mutant receptor
  • Signal transduction

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