2010
DOI: 10.1139/y10-078
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The influence of affinity, efficacy, and slope factor on the estimates obtained by the receptorial responsiveness method (RRM): a computer simulation study

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 inv… Show more

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Cited by 12 publications
(50 citation statements)
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“…The model of RRM is a simplified mathematical description of the co-action of two agonists (evoking the same response of a biological system), if one of these agonists exerts its effect prior to the other one, and the former effect is disregarded (thereby causing a "bias") [11,14]. RRM has been originally developed as a concentration determining method that is based on the fitting of its model (Equation (2)) to an E/c curve that was constructed in the presence of a "biasing" concentration that is to be determined.…”
Section: Discussionmentioning
confidence: 99%
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“…The model of RRM is a simplified mathematical description of the co-action of two agonists (evoking the same response of a biological system), if one of these agonists exerts its effect prior to the other one, and the former effect is disregarded (thereby causing a "bias") [11,14]. RRM has been originally developed as a concentration determining method that is based on the fitting of its model (Equation (2)) to an E/c curve that was constructed in the presence of a "biasing" concentration that is to be determined.…”
Section: Discussionmentioning
confidence: 99%
“…It should be noted that the traditional methods to determine receptor reserve have not proved to be useful for adenosine due to the short half-life of adenosine [33], although receptor reserve values in the cardiac adenosinergic system seem to be of importance, even in terms of diagnostic aspects [34]. Finally, of course, data that were obtained with RRM can serve as input data for in silico investigations dealing with the RRM itself [14,15], and with the adenosinergic mechanisms in the atrial myocardium [35,36].…”
Section: Discussionmentioning
confidence: 99%
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“…The biased adenosine E/c curves were not suitable for the assessment of A 1 adenosine receptor reserve, the goal of the present study. Therefore, effects of adenosine E/c curves biased by NBTI were corrected by means of RRM, our method validated for quantifying changes in agonist concentrations in the microenvironment of the receptors (Gesztelyi et al 2004;Grenczer et al 2010aGrenczer et al , 2010b.…”
Section: Strategy Of the Mathematical Correctionmentioning
confidence: 99%
“…Because NBTI strongly affects the fate of exogenous adenosine used to generate an E/c curve (Szentmiklosi et al 1982;Gesztelyi et al 2003a), adenosine could not be used as an agonist for the E/c curves essential for RRM (Karsai et al 2006). However, RRM enables replacement of a degradable agonist with a stable one (Gesztelyi et al 2004;Grenczer et al 2010aGrenczer et al , 2010b. Thus, the surplus interstitial adenosine accumulated by NBTI was quantified using E/c curves generated with CPA, an A 1 receptor agonist with a significantly longer half-life in living tissues than adenosine (see Eq.…”
Section: Strategy Of the Mathematical Correctionmentioning
confidence: 99%