Abstract
The uptake, metabolism and efflux of 14C-5-hydroxytryptamine (5-HT) were studied in isolated rat lungs, artificially ventilated and perfused via the pulmonary artery with Krebs' medium containing 5 mM glucose and 4.5% bovine serum albumin. Infusion of 0.11 to 17 µM 14C-5-HT resulted in concentration of radioactivity in the lungs. The uptake was a saturable process with the same Km and Vmax whether the main product found in the lungs was 5-hydroxyindoleacetic acid (control conditions) or 5-HT (treatment with iproniazid, an inhibitor of monoamine oxidase). This finding indicates that the rate-limiting step in the uptake of 14C-5-HT was its intracellular transport, not its subsequent metabolism. Once taken up, 14C-5-HT was located in the soluble fraction of lung homogenate. Cocaine, imipramine, chlorpromazine and cold markedly inhibited the pulmonary uptake of 14C-5-HT; anoxia, norepinephrine and tryptamine had only a partial inhibitor effect. Pretreatment with reserpine or perfusion with glucose-free medium had no effect on the uptake. Changes in the ionic composition of the medium were also studied: the absence of Na+ resulted in nearly complete inhibition of concentration of 14C-5-HT in the lungs, and lowered Na+, as well as increased K+, caused a decrease in the affinity of the transport system for 14C-5-HT. Ouabain at 10-3 M had only a partial inhibitory effect. The efflux of 14C-5-HT from the lungs was accelerated by cocaine, imipramine or chlorpromazine, by the absence of extracellular Na+ and by low extracellular Na+. These results indicate that the mechanisms of uptake of 5-HT by perfused lungs, platelets and brain are similar and compatible with the model of Na+-dependent transport; however, the lungs, unlike the other cellular systems, do not store 5-HT, but metabolize it rapidly.
Footnotes
- Received June 14, 1971.
- Accepted May 12, 1972.
- © 1972 by The Williams & Wilkins Co.
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