ESTIMATION OF RATE CONSTANTS FOR SEROTONIN UPTAKE AND COMPARTMENTATION IN NORMAL HUMAN PLATELETS

Biochemical and pharmacological experiments led to a model describing a thrombin-releasable (vesicular) compartment and two non-thrombin-rel easable compartments for 5-hydroxytryptamine (5-HT, serotonin) in norm al human platelets (J. L. Costa, K. L. Kirk, D. L. Murphy, and H. Star k. Br. J. Pharmacol. 72: 449-459, 1981). With tritiated 5-HT as substr ate, the amounts of total and nonreleasable intraplatelet tritiated ma terial were measured. Moreover, in the last set of experiments, the am ounts of extraplatelet tritiated material and extraplatelet tritiated 5-HT were also measured. With these data, identification of the kineti c constants for movement between the various compartments was possible . A recent extension of the similarity transformation approach to nonl inear compartmental models was used to carry out the a priori identifi ability analysis. Then numerical identification was performed by imple menting and achieving: efficient methods from optimal control theory. Under owl experimental conditions, the main results are as follows: 1) the vesicular compartment corresponds to the platelet storage 5-HT co mpartment, 2) instead of pools I and II proposed previously, only a si ngle nonreleasable thrombin-resistant pool could be detected, and 3) t he optimized model computed to suit the first set of experiments fits homologous intraplatelet results obtained under similar experimental c onditions in the last set of experiments and also fits one of the two supplementary extraplatelet investigations.