Kinetics of serotonin uptake in isolated rabbit lungs

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 K(m) and V(max) of ~ 0.84 μM and 0.21 nmol · s^-1 · g wet lung wt^-1. The K(m) 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 V(max)/K(m) was identifiable. V(max)/K(m) values for the high- and low-affinity pathways were ~ 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.