Mathematical modeling of serotonin compartmentation in normal human platelets
Abstract
The movement of radiolabelled 5-hydroxytryptamine (5-HT, serotonin) and its by-products between the extracellular medium, the thrombin-releasable (vesicular) compartment and the non-thrombin-releasable compartment(s) has been investigated in normal human platelets. Using the data obtained, identification of the kinetic constants for movement between the various compartments was possible. For carrying out the a priori identifiability analysis, a recent extension of similarity transformation approach to nonlinear compartmental models was used. Then numerical identification was performed by implementing and achieving efficient methods coming from optimal control theory. Under our experimental conditions, the main results achieved are the following : the vesicular compartment corresponds to the platelet storage 5-HT compartment - instead of the pools I and II proposed previously only a single non-releseable thrombin-resistant pool could be detected and - the optimized model computed to suit the first set of experiments fits subsequent results obtained under similar experimental conditions.