Biomaterial Database

A dispersion model for cellular signal transduction cascades. 2002

Murali Ramanathan

Department of Pharmaceutical Sciences, State University of New York at Buffalo, 14260-1200, USA. murali@acsu.buffalo.edu

OBJECTIVE The purpose of this study was to evaluate the ability of the dispersion model to describe pharmacokinetic-pharmacodynamic data containing contributions from signal transduction cascades. METHODS The partial differential equations and appropriate boundary conditions describing the dispersion model for signal transduction were obtained. Explicit analytical solutions to the dispersion equation were not available, and a numerical approach was necessary. Solutions were obtained by numerical inversion of the output Laplace transform. Generalized least square fitting was used to obtain parameter estimates for a variety of experimental data sets. RESULTS The parameters of the dispersion model estimate the relative roles of diffusion, convection, and chemical reaction in signal transduction. The model is capable of describing messenger RNA and protein expression kinetics induced by drug action. CONCLUSIONS The dispersion model may find potential applications in pharmacokinetic-pharmacodynamic models involving delayed drug effects mediated by transcriptional changes.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal