Modelling of signalling via G-protein coupled receptors: pathway-dependent agonist potency and efficacy.
A mathematical model is constructed to study promiscuous coupling of receptors to G-proteins and to simulate events leading to the activation of multiple effector pathways within a cell. The model is directed at a better understanding of the factors that determine the efficacy and potency of a drug. Assuming that the receptors can exist in multiple conformational states, and allowing for agonist specific conformation, a system of ordinary differential equations is constructed and subsequently pathway-dependent agonist efficacy and potency order is predicted. A simple case of the compartmentalization of receptors and G-proteins is also given, using the current model to illustrate the effects of spatial heterogeneity on the predicted response.
Chen
C Y
CY
Centre for Mathematical Medicine, Division of Theoretical Mechanics, School of Mathematical Science, The University of Nottingham, Nottingham, UK. april.chen@nottingham.ac.uk
Cordeaux
Y
Y
Hill
S J
SJ
King
J R
JR
D019204:GTP-Binding Proteins / Q000502:physiology*; D007700:Kinetics; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins