Metabolism of 5-hydroxytryptophan in the isolated perfused rat lung.
The metabolism of 5-hydroxytryptophan (5-HTP) and tryptophan (TRP) in a single pass across the pulmonary circulation was studied in the isolated ventilated perfused rat lung and by high pressure liquid chromatography. The metabolism of 5-HTP was dependent on the rate of lung perfusion and the duration of infusion of 5-HTP, and was a saturable process with an apparent Km of 1.8 mM and Vmax of 0.14 mumol/g/3 min. The indoles found in the lung were 5-HTP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA); only 5-HIAA was detected in the lung effluent. The efflux of 5-HTP from the lung had two exponential components with half-lives of 0.15 and 3.65 min. After an infusion of 3H-5-HTP, the radiolabel that accumulated in lung was located mainly in the soluble fraction. An infusion of TRP resulted in the synthesis of 5-HTP, 5-HT and 5-HIAA in the lung, and 5-HTP was detected in the lung effluent. The results suggest that 5-HT can be synthesized in the intact lung from circulating TRP and 5-HTP. Since the rate of lung metabolism is low and no 5-HT is released into the lung effluent, the contribution of the lung to circulating levels of 5-HT is likely to be insignificant. Synthesis of 5-HT in intact lung suggests an intrapulmonary role for 5-HT.
Ben-Harari
R R
RR
Department of Anesthesiology, NYU Medical Center, N.Y.
Parent Ermini
A
A
Kleinerman
J
J
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan