Effect of volatile anesthetics on endogenous tryptophan, 5-hydroxytryptophan and 5-hydroxytryptamine in rat lung.

Volatile anesthetics inhibit the pulmonary inactivation of 5-hydroxytryptamine (5-HT) possibly via an effect on endogenous lung 5-HT. The consequent higher systemic arterial 5-HT concentrations may predispose the heart to dysrhythmias. The direct effect of the anesthetics on endogenous 5-HT, its metabolites, and precursors in the isolated ventilated perfused rat lung was determined by high-pressure liquid chromatography. Halothane (0.45, 1.4, and 2.3 minimum alveolar concentration (MAC] and 35% nitrous oxide (N2O) increased lung 5-HT (11, 70, 94, and 54% respectively). The effect of 0.45 MAC halothane and 35% N2O on 5-HT was synergistic. Isoflurane (2.9 MAC) had no effect on lung 5-HT. The lung concentration of tryptophan (TRP) was increased 51% by 2.9 MAC isoflurane, but the rate of efflux of TRP from the lung was unchanged. There was no effect of the anesthetics on 5-hydroxytryptophan (5-HTP). The ratio of 5-HT:5-HTP was significantly increased by 2.3 MAC halothane and 0.5 MAC halothane +35% N2O. The 5-HTP:TRP ratio was unchanged. The metabolite of 5-HT, 5-hydroxyindole acetic acid (5-HIAA), was not always detected. The results suggest that the increase in lung 5-HT by halothane reflects an increase in 5-HTP decarboxylase activity and that halothane and isoflurane exert selective effects on lung 5-HT synthesis. The results do not support the hypothesis that lung 5-HT controls the inactivation of 5-HT in the pulmonary circulation.

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.