AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 3 1061-R1075, Copyright © 1994 by American Physiological Society
Estimation of rate constants for serotonin uptake and compartmentation in normal human platelets
G. Launay, J. L. Costa, M. Da Prada and J. M. Launay
Institut National de Recherche en Informatique et en Automatique, Le Chesnay, France.
Biochemical and pharmacological experiments led to a model describing a
thrombin-releasable (vesicular) compartment and two non-thrombin-releasable
compartments for 5-hydroxytryptamine (5-HT, serotonin) in normal human
platelets (J. L. Costa, K. L. Kirk, D. L. Murphy, and H. Stark. Br. J.
Pharmacol. 72: 449-459, 1981). With tritiated 5-HT as substrate, the
amounts of total and nonreleasable intraplatelet tritiated material were
measured. Moreover, in the last set of experiments, the amounts of
extraplatelet tritiated material and extraplatelet tritiated 5-HT were also
measured. With these data, identification of the kinetic constants for
movement between the various compartments was possible. A recent extension
of the similarity transformation approach to nonlinear compartmental models
was used to carry out the a priori identifiability analysis. Then numerical
identification was performed by implementing and achieving efficient
methods from optimal control theory. Under our experimental conditions, the
main results are as follows: 1) the vesicular compartment corresponds to
the platelet storage 5-HT compartment, 2) instead of pools I and II
proposed previously, only a single nonreleasable thrombin-resistant pool
could be detected, and 3) the optimized model computed to suit the first
set of experiments fits homologous intraplatelet results obtained under
similar experimental conditions in the last set of experiments and also
fits one of the two supplementary extraplatelet investigations.
