Precursor utilization of 5-hydroxytryptophan for 5-hydroxytryptamine biosynthesis in isolated and perfused rabbit and rat lungs

Abstract

The present study was designed to investigate whether lungs can utilize 5-hydroxytryptophan (5-HTP), formed elsewhere and transported, for the synthesis of 5-hydroxytryptamine (5-HT). [14C]5-HTP uptake was 7.7 ± 1.1 and 3.9 ± 0.2% by rabbit and rat lungs, respectively, after 1 h of perfusion with 10 μM [14C]5-HTP. There was an increase in the lung uptake of [14C]5-HTP when the lungs were preperfused with 0.5 mM chlorphentermine (CP) and the uptake was low when the lungs were preperfused with 0.1 mM hydroxybenzylhydrazine dihydrochloride (HBH). The perfusate concentration of 5-hydroxyindole acetic acid (5-HIAA) increased significantly (3–4 μg/100 mL) during rabbit lung perfusion with 10 μM [14C]5-HTP and this did not change significantly when the lungs were preperfused with 0.5 mM CP. However, 5-HT increased with time in the perfusate, 5-HT, but not 5-HIAA, was detected in the perfusate and increased with time of perfusion when the rat lungs were perfused either with 10 μM 5-HTP or with 0.5 mM CP and 10 μM 5-HTP. However, no metabolites were detected in either the rabbit lung or rat lung perfusates when they were preperfused with 0.1 mM HBH. Lung contents of 5-HT and 5-HIAA were significantly higher in the rat lungs and only 5-HIAA increased in rabbit lungs after 1 h of perfusion with 10 μM 5-HTP. Preperfusion with 0.5 mM CP resulted in a greater increase in the 5-HT content of both rabbit and rat lungs. When the lungs were preperfused with 0.1 mM HBH, [14C]5-HT formation from [14C]5-HTP was obtunded. Homogenates of rabbit and rat lungs incubated with [14C]5-HTP (10 μM) resulted in the formation of substantial amounts of [14C]5-HT and [14C]5-HIAA. Incubations with CP (0.5 or 1 mM) resulted in significant increases of 5-HT levels and a corresponding significant reduction in 5-HIAA levels. On the other hand, incubations with HBH (0.1 mM) resulted in significant inhibition of 5-HT and 5-HIAA formation. 5-HT formation from 5-HTP by rat and rabbit lungs in in vitro incubations is in consonance with the perfusion experiments. These results provide evidence that lung can synthesize 5-HT from the circulating 5-HTP, and pulmonary contribution of 5-HT to the circulating levels is possible.