Heuther G, Hajak G, Reimer A, Poeggeler B, Blömer M, Rodenbeck A, Rüther E
Department of Psychiatry, University of Göttingen, Federal Republic of Germany.
Psychopharmacology (Berl). 1992;109(4):422-32. doi: 10.1007/BF02247718.
L-Tryptophan (Trp) was widely used as a natural tool for the support of serotonin-mediated brain functions and as a challenge probe for the assessment of serotonin-mediated neuroendocrine responses. The metabolic fate of the administered Trp and the kinetics of the accumulation of Trp metabolites in the circulation, however, have never thoroughly been investigated. This study describes the time- and dose-dependent alterations in the plasma levels of various Trp metabolites and large neutral amino acids after the infusion of Trp to healthy young men (1, 3 and 5 g; placebo-controlled, double-blind, cross-over study during day- and night-time). The major Trp metabolites (kynurenine, indole acetic acid and indole lactic acid) in plasma increased dose-dependently but rather slowly after Trp administration to reach their maximal plasma levels (up to 10-fold after the 5 g dose) at about 3 h p.i., and remained at an elevated level (about 5-fold) for up to 8 h. N-acetyl-Trp and 5-hydroxy-Trp rose rapidly and massively after Trp infusions, at the 5 g dose more than 200- and 20-fold, respectively, and declined rapidly to about 5-fold baseline levels within 2 h. Whole blood serotonin levels were almost unaffected by the Trp infusions. A rather slow increase of 5-hydroxyindole acetic acid was seen, reaching maximum values (3-fold at the 5 g dose) at about 2 h after the infusion of Trp. Additionally, a dose-dependent rise of circulating melatonin was observed after L-Trp infusions. The administration of L-Trp caused a depletion of the concentrations of the other large neutral amino acids and a dose dependent decrease of the ratio between plasma tyrosine and the sum of the plasma concentrations of the other large neutral amino acids. Apparently, none of the existing pathways of peripheral Trp metabolism is saturated by its substrate, Trp in men. At least some of the central effects reported after L-Trp administration may be mediated by the Trp-stimulated formation of neuroactive metabolites or by the decreased availability of tyrosine for catecholamine synthesis.
L-色氨酸（Trp）被广泛用作支持血清素介导的脑功能的天然工具，以及评估血清素介导的神经内分泌反应的激发探针。然而，所给予的Trp的代谢命运以及Trp代谢产物在循环中的积累动力学从未得到彻底研究。本研究描述了在向健康年轻男性输注Trp（1、3和5克；安慰剂对照、双盲、昼夜交叉研究）后，各种Trp代谢产物和大中性氨基酸血浆水平随时间和剂量的变化。血浆中的主要Trp代谢产物（犬尿氨酸、吲哚乙酸和吲哚乳酸）在给予Trp后呈剂量依赖性增加，但增加较为缓慢，在注射后约3小时达到最大血浆水平（5克剂量后高达10倍），并在长达8小时内保持在升高水平（约5倍）。N-乙酰-Trp和5-羟基-Trp在输注Trp后迅速大量升高，5克剂量时分别超过200倍和20倍，在2小时内迅速降至约5倍基线水平。全血血清素水平几乎不受Trp输注的影响。观察到5-羟基吲哚乙酸升高较为缓慢，在输注Trp后约2小时达到最大值（5克剂量时为3倍）。此外，输注L-Trp后观察到循环褪黑素呈剂量依赖性升高。给予L-Trp导致其他大中性氨基酸浓度降低，以及血浆酪氨酸与其他大中性氨基酸血浆浓度总和之间的比例呈剂量依赖性下降。显然，男性外周Trp代谢现有的任何途径都未被其底物Trp饱和。L-Trp给药后报道的至少一些中枢效应可能是由Trp刺激形成神经活性代谢产物或由儿茶酚胺合成中酪氨酸可用性降低介导的。
