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The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy.

Publication ,  Journal Article
Weiss, JM; Morgan, PH; Lutz, MW; Kenakin, TP
Published in: J Theor Biol
August 21, 1996

Early work in pharmacology characterized the interaction of receptors and ligands in terms of two parameters, affinity and efficacy, an approach we term the bipartite view. A precise formulation of efficacy only exists for very simple pharmacological models. Here we extend the notion of efficacy to models that incorporate receptor activation and G-protein coupling. Using the cubic ternary complex model, we show that efficacy is not purely a property of the ligand-receptor interaction; it also depends upon the distributional details of the receptor species in the native receptor ensemble. This suggests a distinction between what we call potential efficacy (a vector) and realized efficacy (a scalar). To each receptor species in the native receptor ensemble we assign a part-worth utility; taken together these utilities comprise the potential efficacy vector. Realized efficacy is the expectation of these part-worth utilities with respect to the frequency distribution of receptor species in the native receptor ensemble. In the parlance of statistical decision theory, the binding of a ligand to a receptor ensemble is a random prospect and realized efficacy is the utility of this prospect. We explore the implications that our definition of efficacy has for understanding agonism and in assessing the legitimacy of the bipartite view in pharmacology.

Duke Scholars

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Published In

J Theor Biol

DOI

ISSN

0022-5193

Publication Date

August 21, 1996

Volume

181

Issue

4

Start / End Page

381 / 397

Location

England

Related Subject Headings

  • Stimulation, Chemical
  • Receptors, Cell Surface
  • Protein Binding
  • Models, Chemical
  • Ligands
  • Humans
  • Evolutionary Biology
  • 49 Mathematical sciences
  • 31 Biological sciences
  • 08 Information and Computing Sciences
 

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Weiss, J. M., Morgan, P. H., Lutz, M. W., & Kenakin, T. P. (1996). The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy. J Theor Biol, 181(4), 381–397. https://doi.org/10.1006/jtbi.1996.0139
Weiss, J. M., P. H. Morgan, M. W. Lutz, and T. P. Kenakin. “The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy.J Theor Biol 181, no. 4 (August 21, 1996): 381–97. https://doi.org/10.1006/jtbi.1996.0139.
Weiss JM, Morgan PH, Lutz MW, Kenakin TP. The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy. J Theor Biol. 1996 Aug 21;181(4):381–97.
Weiss, J. M., et al. “The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy.J Theor Biol, vol. 181, no. 4, Aug. 1996, pp. 381–97. Pubmed, doi:10.1006/jtbi.1996.0139.
Weiss JM, Morgan PH, Lutz MW, Kenakin TP. The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy. J Theor Biol. 1996 Aug 21;181(4):381–397.
Journal cover image

Published In

J Theor Biol

DOI

ISSN

0022-5193

Publication Date

August 21, 1996

Volume

181

Issue

4

Start / End Page

381 / 397

Location

England

Related Subject Headings

  • Stimulation, Chemical
  • Receptors, Cell Surface
  • Protein Binding
  • Models, Chemical
  • Ligands
  • Humans
  • Evolutionary Biology
  • 49 Mathematical sciences
  • 31 Biological sciences
  • 08 Information and Computing Sciences