Zagajewski J, Wojcik-Grzybek D, Brzozowski B, Majka J, Magierowski M, Placha W, Lasota M, Laidler P M, Brzozowski T
Department of Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.
J Physiol Pharmacol. 2021 Dec;72(6). doi: 10.26402/jpp.2021.6.15. Epub 2022 Apr 24.
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine synthesized in vertebrates mainly in the pineal gland, and is known to be involved mainly in thermoregulation and control of the circadian rhythm. That indoleamine can affect the auto-, para- and endocrine pathways, regulating body functions and affecting the metabolism of animals and humans. In addition to the pineal gland, melatonin can be synthesized in many extra-pineal tissues, mainly in the gastrointestinal tract. Previous studies have shown that melatonin plays an important role in the defense system of the gastrointestinal mucosa, demonstrating a protective effect on the gastrointestinal tract and the acceleration of healing of chronic ulcers through the scavenging of reactive oxygen metabolites (ROS) and the activation of protective nitric oxide (NO) and vasodilator neuropeptides released from the sensory afferent neurons. The process of converting the melatonin precursor L-tryptophan into melatonin is already known, but not all aspects of this process for the synthesis of other metabolites of this pathway have been fully elucidated and this issue remains poorly understood. In this study, the conversion of L-tryptophan to melatonin and other metabolites was determined in gastric mucosa collected from rats with or without intragastric (i.g.) melatonin or L-tryptophan administration, both administered at a single dose of 50 mg/kg. For the determination of five metabolites of L-tryptophan: kynurenine, 5-hydroxytryptamine, 5-hydroxytryptophan, anthranilic acid, indole-3-acetic acid together with melatonin, we have modified the previously developed high-performance liquid chromatography (HPLC) method using a native fluorescence detection system and UV-VIS. The obtained results show that: 1) L-tryptophan is converted into melatonin in the gastric mucosa during the day, e.g. after eating a meal containing L-tryptophan, as it was imitated and confirmed by our study, in which this amino acid was administered directly to the stomach, 2) the gastric mucosa is capable of producing melatonin in much greater amounts than those recorded in the blood serum of rats given a single dose of L-tryptophan, and 3) apart from melatonin, the only serum levels of these five metabolites of the L-tryptophan metabolic pathway are detectable, while their level in the gastric mucosa is low and barely detectable under physiological conditions. Our present observations support the notion that the gastric mucosa is one of the main sources of melatonin production from L-tryptophan outside the pineal gland.
褪黑素（N-乙酰-5-甲氧基色胺）是一种在脊椎动物体内主要由松果体合成的吲哚胺，已知其主要参与体温调节和昼夜节律的控制。这种吲哚胺可以影响自身、旁分泌和内分泌途径，调节身体功能并影响动物和人类的新陈代谢。除松果体外，褪黑素还可以在许多松果体外组织中合成，主要是在胃肠道。先前的研究表明，褪黑素在胃肠道黏膜的防御系统中发挥重要作用，通过清除活性氧代谢产物（ROS）以及激活由感觉传入神经元释放的保护性一氧化氮（NO）和血管舒张神经肽，对胃肠道表现出保护作用并加速慢性溃疡的愈合。将褪黑素前体L-色氨酸转化为褪黑素的过程已经为人所知，但该途径中其他代谢产物合成过程的所有方面尚未完全阐明，这个问题仍然知之甚少。在本研究中，测定了在给予或未给予胃内（i.g.）褪黑素或L-色氨酸（均以50mg/kg的单剂量给药）的大鼠收集的胃黏膜中L-色氨酸向褪黑素和其他代谢产物的转化情况。为了测定L-色氨酸的五种代谢产物：犬尿氨酸、5-羟色胺、5-羟色氨酸、邻氨基苯甲酸、吲哚-3-乙酸以及褪黑素，我们改进了先前开发的使用天然荧光检测系统和紫外可见分光光度计的高效液相色谱（HPLC）方法。获得的结果表明：1）L-色氨酸在白天可在胃黏膜中转化为褪黑素，例如在摄入含有L-色氨酸的食物后，正如我们的研究所模拟和证实的那样，其中这种氨基酸是直接给予胃内；2）胃黏膜产生褪黑素的量比给予单剂量L-色氨酸的大鼠血清中记录的量要多得多；3）除褪黑素外，L-色氨酸代谢途径的这五种代谢产物仅在血清中可检测到，而在生理条件下它们在胃黏膜中的水平很低且几乎检测不到。我们目前的观察结果支持这样一种观点，即胃黏膜是松果体外L-色氨酸产生褪黑素的主要来源之一。
