The influence of affinity, efficacy, and slope factor on the estimates obtained by the receptorial responsiveness method (RRM): A computer simulation study

Maria Grenczer, Akos Pinter, Judit Zsuga, Adam Kemeny-Beke, Bela Juhasz, Peter Szodoray, Arpad Tosaki, Rudolf Gesztelyi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The receptorial responsiveness method (RRM) was proposed to characterize changes in the concentration of degradable agonists in the microenvironment of their receptors. The characterization is done by providing concentrations of a stable agonist for the same receptor that is equieffective with the change in concentration to be characterized. RRM is based on the analysis of concentration-effect (E/c) curves reflecting the simultaneous action of the degradable and the stable agonist. In the present study, we investigated whether dissimilar affinity and (or) efficacy of the coacting agonists as well as the steepness of the E/c curves influence the reliability of RRM. E/c curves were simulated based on the operational model and then analyzed with RRM. We found that dissimilarity in affinity of the coacting agonists did not affect the accuracy of RRM estimates. In contrast, accuracy of the estimation depended on the magnitude of the concentration to be assessed, the operational slope factor, and the operational efficacy ratio of the coacting agonists. However, our results suggest that proper choice of a stable agonist for a degradable one can help to ensure reliable results, since information about the change in concentration of a degradable agonist is otherwise difficult to obtain.

Original languageEnglish
Pages (from-to)1061-1073
Number of pages13
JournalCanadian journal of physiology and pharmacology
Volume88
Issue number11
DOIs
Publication statusPublished - Nov 1 2010

Keywords

  • Affinity
  • Concentration estimation
  • Efficacy
  • RRM
  • Receptorial responsiveness method
  • Slope

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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