Kinetics versus equilibrium: the importance of GTP in GPCR activation

Trends Pharmacol Sci. 1999 Dec;20(12):477-81. doi: 10.1016/s0165-6147(99)01394-2.


Agonist-bound G-protein-coupled receptors (GPCRs) facilitate GDP-GTP exchange on their cognate G proteins. The binding properties of GPCRs are adequately described by the ternary complex model. However, in this article a more realistic (steady-state) model, which is necessary to describe the catalytic effect of agonist-bound receptors on G-protein activation, will be discussed. This model predicts that agonist potency and efficacy might vary from tissue to tissue, depending on the G-protein concentration and can be extended to explain why an agonist's ability to increase the receptor's affinity for empty G proteins (in the absence of GTP) is related to the agonist's efficacy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • GTP-Binding Proteins / metabolism*
  • Guanosine Triphosphate / metabolism*
  • Models, Biological
  • Models, Theoretical
  • Receptors, Cell Surface / metabolism*
  • Thermodynamics


  • Receptors, Cell Surface
  • Guanosine Triphosphate
  • GTP-Binding Proteins