Journal of Applied Physiology, Vol 66, Issue 5 2328-2337, Copyright © 1989 by American Physiological Society
Kinetics of serotonin uptake in isolated rabbit lungs
F. A. Peeters, T. A. Bronikowski, C. A. Dawson, J. H. Linehan, H. Bult and A. G. Herman
Division of Pharmacology, University of Antwerp, Wilrijk, Belgium.
The single-pass, bolus-injection method was used to study the effect of
serotonin (5-HT) concentration on the extraction of 5-HT by isolated
perfused rabbit lungs. The extraction pattern suggested that an uptake
model, which includes multiple parallel uptake processes, provided a better
representation of the data than the simple Michaelis-Menten equation, which
has commonly been used to fit the saturable uptake data in previous
studies. In particular, the rabbit lung data could be fit with two such
parallel pathways. Since the 5-HT uptake could virtually be completely
blocked by imipramine, both pathways can be considered to be
carrier-mediated processes. The high-affinity pathway was saturable within
the range of concentrations studied, with a Km and Vmax of approximately
0.84 microM and 0.21 nmol.s-1.g wet lung wt-1. The Km for the low-affinity
pathway was larger than concentrations for which accurate uptake
measurements are practical in the perfused organ. Thus, for the
low-affinity pathway, only Vmax/Km was identifiable. Vmax/Km values for the
high- and low-affinity pathways were approximately 2.87 and 0.35 ml/s,
respectively. The results suggest that it will be worthwhile to investigate
the behavior of these uptake parameters in response to changes in lung
physiology and endothelial function in future studies.
