Journal of Applied Physiology, Vol 57, Issue 3 720-730, Copyright © 1984 by American Physiological Society
Lung serotonin uptake kinetics from indicator-dilution and constant-infusion methods
C. M. Malcorps, C. A. Dawson, J. H. Linehan, T. A. Bronikowski, D. A. Rickaby, A. G. Herman and J. A. Will
The kinetics of the pulmonary endothelial uptake of serotonin (5-HT) were
evaluated in isolated dog lung lobes using three methods. In method A
serotonin was infused at various constant rates to provide a range of
capillary concentrations that included Km. The arterial and venous
concentrations measured by high-performance liquid chromatography were then
used to determine the effect of concentration on the rate of 5-HT uptake.
In method B trace doses of 5-[3H]HT and a reference indicator (indocyanine
green dye) were injected during each constant infusion of unlabeled 5-HT to
provide a measure of unidirectional 5-HT uptake at each background
concentration. In method C boluses containing different amounts of
unlabeled 5-HT, along with the 5-[3H]HT and the dye, were injected such
that each bolus resulted in a range of concentrations and provided a
measure of the unidirectional uptake at each concentration. Each method
provided the data needed to calculate the maximum uptake rate (Vmax) and
the concentration at Vmax/2 (Km), assuming that the uptake kinetics can be
represented by the Michaelis-Menten equation. However, the mathematical
model underlying each method involved different assumptions about the
returning flux of the 5-HT which entered the endothelial cell and the
heterogeneity of vascular transit times. The results obtained, considered
in light of the different assumptions involved, indicate that all three
methods can provide reasonable estimates of the mass transfer kinetic
constants if the constant infusions of 5-HT are of short duration and/or
the boluses are adequately dispersed prior to reaching the capillary bed.
