Effect of asymmetry of concentration-response curves on the results obtained by the receptorial responsiveness method (RRM): An in silico study

Maria Grenczer, Judit Zsuga, Laszlo Majoros, Akos Pinter, Adam Kemeny-Beke, B. Juhász, A. Tósaki, R. Gesztelyi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The receptorial responsiveness method (RRM) was proposed to estimate changes in the concentration of an agonist in the microenvironment of its receptor. Usually, this is done by providing the equieffective concentration of another agonist for the same receptor or for a largely overlapping postreceptorial signaling ("test agonist"). The RRM is a special nonlinear regression algorithm to analyze a concentration-response (E/c) curve that represents the simultaneous actions of a single agonist concentration to be estimated and of increasing concentrations of the test agonist. The aim of this study was to explore whether asymmetry of the E/c curve to be analyzed influences the reliability of the RRM. For this purpose, computer simulation was performed by constructing symmetric and asymmetric E/c curves using the operational model of agonism, and then these curves were analyzed with the RRM. To perform the RRM, 2 types of equations were used: one involving the Hill equation, the simplest model of the E/c relationship, and one containing the Richards equation, an advanced model properly handling E/c curve asymmetry. Results of this study indicate that E/c curve asymmetry does not significantly influence the accuracy of the estimates provided by the RRM. Thus, when using the RRM, it is not necessary to replace the Hill equation with the Richards equation to obtain useful estimates. Furthermore, it was found that estimation of a high concentration of a high-efficacy agonist can fail when the RRM is performed with a low-efficacy test agonist in a system characterized by a small operational slope factor.

Original languageEnglish
Pages (from-to)1074-1083
Number of pages10
JournalCanadian Journal of Physiology and Pharmacology
Volume88
Issue number11
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Computer Simulation
asymmetry
curves
estimates
regression analysis
computerized simulation
slopes

Keywords

  • Concentration estimation
  • Concentration-response curve
  • Efficacy
  • Operational model
  • Receptorial responsiveness method
  • RRM
  • Slope
  • Symmetry

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology
  • Physics and Astronomy(all)

Cite this

Effect of asymmetry of concentration-response curves on the results obtained by the receptorial responsiveness method (RRM) : An in silico study. / Grenczer, Maria; Zsuga, Judit; Majoros, Laszlo; Pinter, Akos; Kemeny-Beke, Adam; Juhász, B.; Tósaki, A.; Gesztelyi, R.

In: Canadian Journal of Physiology and Pharmacology, Vol. 88, No. 11, 11.2010, p. 1074-1083.

Research output: Contribution to journalArticle

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