AJP - Cell Physiology, Vol 248, Issue 1 88-101, Copyright © 1985 by American Physiological Society
Cytoplasmic and nuclear uptake of aldosterone in toad bladder: a mathematical modeling approach
M. Claire, J. L. Steimer, M. E. Oblin, H. P. Gaeggeler, A. Venot, P. Corvol and B. C. Rossier
The mechanism of aldosterone uptake in the epithelial cells of toad bladder
was studied using mathematical modeling. Two complementary approaches were
used. The first involved analysis of cytosolic aldosterone binding at
steady state according to models defined by the sum of independent
noninteractive binding sites. The best model describing the experimental
data corresponded to two specific binding sites with mean dissociation
constant values of 0.20 and 60 nM for types 1 and 2, respectively. The
second approach was based on the analysis of cytoplasmic and nuclear
aldosterone uptake kinetics at 25 and 0 degrees C in intact bladder. Two
models (A and B) were studied. They both implied the existence of two types
of aldosterone binding sites as precursors of the corresponding chromatin
bound complexes. In model A, nuclear translocation of the two types of
receptors was assumed to obey first-order kinetics. In model B, the
translocation process for type 1 sites involved a time lag leading to
delayed binding to chromatin. Both models were found to fit the
experimental data satisfactorily. The fit obtained for model B appeared to
be better at low aldosterone concentrations.
