Kinetics of serotonin uptake in the dog lung

A bolus containing [³H]serotonin and indocyanine green dye was rapidly introduced into the pulmonary artery of an isolated blood-perfused left lower dog lung lobe. Sequential samples of the venous effluent were collected for approximately 25 s following the injections. The lung uptake of the injected [³H]serotonin was inversely proportional to the injected dose, ranging from about 70% for a 10-nmol injection to about 38% for a 100-nmol injection. Less than 2% of the injected ³H, which appeared in the venous effluent over the sampling interval, was in the form of [³H]5-hydroxyindoleacetic acid; and during the bolus transit through the lung lobe, uptake of serotonin by platelets was negligible. The serotonin extraction ratio curves exhibited dose-dependent characteristic shapes that we have interpreted using a model in which it is assumed that serotonin uptake follows Michaelis-Menten kinetics and flow through the capillary bed is heterogeneous. Using this model and a multiple regression analysis, the outflow dye and ³H concentration vs. time curves were used to estimate K(m) and V(max) for serotonin uptake by the lungs.