Scaramellini1997 - Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists

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Model Identifier
BIOMD0000001008
Short description
The two-receptor:one-transducerm odel (Leff, 1987) is here extended to analyze interactions between agonistsd isplaying E/[A] curves of different shapes, by incorporating slope factors into the separate and common parts of the transduction pathway. Interactions were modelled as the effect of one agonist, at fixed concentration, on the curve to the other. A variety of patterns of position and slope changes are predicted. These do not depend on the shape of the control curve, rather, they depend on the slope factors in the separate and common pathways. The following specific predictions are made: (1) when the common pathway is steep, curves undergo potentiation and flattening; (2) when the common pathway is flat, curves undergo right-shift and steepening; (3) when the common pathway is hyperbolic, curves undergo right-shift, with no slope change; (4) when the slope depends on the separate pathways, curves only undergo right-shift with no change in slope. The model provides a sound basis for classifying agonist interactions and for detecting additional, synergistic or antagonistic properties. This analysisin dicatest hat methodsb asedo n dose-additivity or independencea re less reliable for these purposes. The model provides a practical test, based on slope changes, to detect and quantify additional properties
Format
SBML (L2V4)
Related Publication
  • Analysis of agonist-agonist interactions: the crucial influence of curve shape.
  • Scaramellini C, Bennett G, Leff P
  • Journal of pharmacological and toxicological methods , 4/ 1997 , Volume 37 , Issue 3 , pages: 167-178 , PubMed ID: 9253753
  • Department of Pharmacology, Astra Charnwood, Loughborough, Leics, England.
  • The two-receptor:one-transducer model (Leff, 1987) is here extended to analyze interactions between agonists displaying E[A] curves of different shapes, by incorporating slope factors into the separate and common parts of the transduction pathway. Interactions were modelled as the effect of one agonist, at fixed concentration, on the curve to the other. A variety of patterns of position and slope changes are predicted. These do not depend on the shape of the control curve, rather, they depend on the slope factors in the separate and common pathways. The following specific predictions are made: (1) when the common pathway is steep, curves undergo potentiation and flattening; (2) when the common pathway is flat, curves undergo right-shift and steepening; (3) when the common pathway is hyperbolic, curves undergo right-shift, with no slope change; (4) when the slope depends on the separate pathways, curves only undergo right-shift with no change in slope. The model provides a sound basis for classifying agonist interactions and for detecting additional, synergistic or antagonistic properties. This analysis indicates that methods based on dose-additivity or independence are less reliable for these purposes. The model provides a practical test, based on slope changes, to detect and quantify additional properties.
Contributors
Kausthubh Ramachandran

Metadata information

isDescribedBy
is
hasProperty
Mathematical Modelling Ontology MAMO_0000020
C16974

Curation status
Curated

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Model files

Scaramellini1997.xml SBML L2V4 file of Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists 24.89 KB Preview | Download

Additional files

Scaramellini1997.py Python file of SBML L2V4 file of Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists 3.00 KB Preview | Download
Scaramellini1997.sedml SED-ML file of Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists 4.70 KB Preview | Download
Scaramellini1997.omex COMBINE archive of Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists 10.37 KB Preview | Download
Scaramellini1997.cps COPASI 4.30 (Build 240) file of Two-receptor:One-transducer (2R1T) model for analysis of interactions between agonists 58.10 KB Preview | Download

  • Model originally submitted by : Kausthubh Ramachandran
  • Submitted: 08-Jun-2021 10:05:13
  • Last Modified: 08-Jun-2021 10:05:13
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 08-Jun-2021 10:05:13
    • Submitted by: Kausthubh Ramachandran
    • With comment: Automatically added model identifier BIOMD0000001008
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Curator's comment:
(added: 08 Jun 2021, 10:02:22, updated: 08 Jun 2021, 10:04:59)
Fig 1 from the manuscript is reproduced here. The simulation was performed on a Spyder IDE on a Python environment and was plotted using matplotlib.