A Model of Activation and Desensitisation of G-Protein Coupled Receptors
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML model has been recoded to remove the reaction element. The model is known to run in both PCEnv and COR to recreate the published results. The units have been checked and are consistent.
Model Structure
Signalling through G-protein coupled receptors is one of the most common and most important methods of transmitting information to the inside of cells. Many mathematical models have been published to describe this type of signal transduction, but the kinetic model described by Riccobene, Omann and Linderman (1999) is unique in that it includes the dynamics of G-protein activation and desensitisation, in addition to considering active and inactive receptor states (see the figure below). The model was used to predict how different ligands would affect the nature of the signal transduction response.
The complete original paper reference is cited below:
Modeling Activation and Desensitisation of G-Protein Coupled Receptors Provides Insight into Ligand Efficacy, Todd A. Riccobene, Geneva M. Omann and Jennifer J. Linderman, 1999
Journal of Theoretical Biology
, 200, 207-222. (A PDF version of the article is available for Journal Members on the Journal of Theoretical Biology website.) PubMed ID: 10504286
diagram of the reaction pathway
A schematic diagram of Riccobene, Omann and Linderman's model of G-protein coupled receptor signalling. R is the inactive form of the receptor, R* is the active form of the receptor, Rds is the desensitised form of the receptor, L represents the ligand (in this case, N-formyl-norleucyl-leucyl-phenylalaninyl-nor-leucyl-tyrosyl-lysine-fluorescein, or CHO-NLFNTK-fl), G is the inactive G-protein, G* is the activated G-protein, and LR/LR*/LRds represents the ligand/receptor complex in its various forms.
R
inactive receptor
$\frac{d R}{d \mathrm{time}}=\mathrm{kr}\mathrm{LR}+\frac{\mathrm{kfR}}{\mathrm{Kact}}\mathrm{R\_star}-\mathrm{kf}LR+\mathrm{kfR}R$
R_star
active receptor
$\frac{d \mathrm{R\_star}}{d \mathrm{time}}=\mathrm{kr}\mathrm{LR\_star}+\mathrm{kfR}R-\mathrm{alpha}\mathrm{kf}L\mathrm{R\_star}+\frac{\mathrm{kfR}}{\mathrm{Kact}}\mathrm{R\_star}$
LR
inactive ligand-receptor complex
$\frac{d \mathrm{LR}}{d \mathrm{time}}=\mathrm{kf}LR+\frac{\mathrm{kfR}}{\mathrm{alpha}\mathrm{Kact}}\mathrm{LR\_star}-\mathrm{kr}\mathrm{LR}+\mathrm{kfR}\mathrm{LR}$
LR_star
active ligand-receptor complex
$\frac{d \mathrm{LR\_star}}{d \mathrm{time}}=\mathrm{kfR}\mathrm{LR}+\mathrm{alpha}\mathrm{kf}L\mathrm{R\_star}-\frac{\mathrm{kfR}}{\mathrm{alpha}\mathrm{Kact}}\mathrm{LR\_star}+\mathrm{kds}\mathrm{LR\_star}+\mathrm{kr}\mathrm{LR\_star}$
LR_ds
desensitised ligand-receptor complex
$\frac{d \mathrm{LR\_ds}}{d \mathrm{time}}=\mathrm{kds}\mathrm{LR\_star}+\mathrm{kf2}L\mathrm{R\_ds}-\mathrm{kr2}\mathrm{LR\_ds}$
R_ds
desensitised receptor
$\frac{d \mathrm{R\_ds}}{d \mathrm{time}}=\mathrm{kr2}\mathrm{LR\_ds}-\mathrm{kf2}L\mathrm{R\_ds}$
G_star
activated G-protein
$\frac{d \mathrm{G\_star}}{d \mathrm{time}}=\mathrm{ka}G(\mathrm{LR\_star}+\mathrm{R\_star})-\mathrm{ki}\mathrm{G\_star}$
G
inactive G-protein
$\frac{d G}{d \mathrm{time}}=\mathrm{ki}\mathrm{G\_star}-\mathrm{ka}G(\mathrm{LR\_star}+\mathrm{R\_star})$
L
ligand
The University of Auckland, Bioengineering Institute
1999-09-21
2002-10-18T00:00:00+00:00
Catherine
Lloyd
May
Riccobene, Omann and Linderman's 1999 model of the activation and
desensitisation of G-protein coupled receptors.
2003-04-09
Added publication date information.
This is the CellML descripition of Riccobene, Omann and Linderman's
1999 model of the activation and desensitisation of G-protein coupled
receptors.
Autumn
Cuellar
A
Geneva
Omann
M
c.lloyd@auckland.ac.nz
Catherine Lloyd
The University of Auckland
The Bioengineering Institute
keyword
pharmacology
desensitisation
efficacy
signal transduction
gpcr
g-protein
Catherine
Lloyd
May
Todd
Riccobene
A
Jennifer
Linderman
J
Catherine Lloyd
Modeling Activation and Desensitisation of G-Protein Coupled
Receptors Provides Insight into Ligand Efficacy
200
207
222
2008-01-03T10:14:55+13:00
Recoded model to remove the reaction element.
Journal of Theoretical Biology
This CellML model has been recoded to remove the reaction element. The model is known to run in both PCEnv and COR to recreate the published results. The units have been checked and are consistent.
10504286