Precursor utilization of 5-hydroxytryptophan for 5-hydroxytryptamine biosynthesis in isolated and perfused rabbit and rat lungs.
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 microM [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 micrograms/100 mL) during rabbit lung perfusion with 10 microM [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 microM 5-HTP or with 0.5 mM CP and 10 microM 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 microM 5-HTP. Preperfusion with 0.5 mM CP resulted in a greater increase in the 5-HT content of both rabbit and rat lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
D006916:5-Hydroxytryptophan / Q000493:pharmacokinetics*; D000818:Animals; D002745:Chlorphentermine / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis*
D006834:Hydrazines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D002745:Chlorphentermine