PDF(Pubmed)
Abstract：
Tryptophan is an essential amino acid and plays an important role in several metabolic processes relevant for the human health. As the main metabolic pathway for tryptophan along the kynurenine axis is involved in inflammatory responses, changed metabolite levels can be used to monitor inflammatory diseases such as ulcerative colitis. As a progenitor of serotonin, altered tryptophan levels have been related to several neurogenerative diseases as well as depression or anxiety. While tryptophan concentrations are commonly evaluated in serum, a non-invasive detection approach using saliva might offer significant advantages, especially during long-term treatments of patients or elderly. In order to estimate whether active transport processes for tryptophan might contribute to a potential correlation between blood and saliva tryptophan concentrations, we investigated tryptophan\'s transport across an established oral mucosa in vitro model. Interestingly, treatment with tryptophan revealed a concentration dependent secretion of tryptophan and the presence of a saturable transporter while transport studies with deuterated tryptophan displayed increased permeability from the saliva to the blood compartment. Protein analysis demonstrated a distinct expression of L-type amino acid transporter 1 (LAT1), the major transporter for tryptophan, and exposure to inhibitors (2 -amino-2-norbornanecarboxylic acid (BCH), L-leucine) led to increased tryptophan levels on the saliva side. Additionally, exposure to tryptophan in equilibrium studies resulted in a regulation of LAT1 at the mRNA level. The data collected in this study suggest the participation of active transport mechanisms for tryptophan across the oral mucosa epithelium. Future studies should investigate the transport of tryptophan across salivary gland epithelia in order to enable a comprehensive understanding of tryptophan exchange at the blood-saliva barrier.
摘要：
色氨酸是一种必需氨基酸，在与人类健康相关的几种代谢过程中起着重要作用。由于色氨酸沿犬尿氨酸轴的主要代谢途径参与炎症反应，改变代谢产物水平可用于监测炎症性疾病如溃疡性结肠炎。作为血清素的祖先，色氨酸水平的改变与几种神经退行性疾病以及抑郁或焦虑有关。虽然通常在血清中评估色氨酸浓度，使用唾液的非侵入性检测方法可能会提供显着的优势，特别是在患者或老年人的长期治疗期间。为了评估色氨酸的主动转运过程是否可能导致血液和唾液色氨酸浓度之间的潜在相关性，我们研究了色氨酸在建立的口腔黏膜体外模型中的转运。有趣的是,色氨酸治疗显示色氨酸的浓度依赖性分泌和可饱和转运蛋白的存在，而氘代色氨酸的转运研究显示从唾液到血液隔室的渗透性增加。蛋白质分析表明L型氨基酸转运蛋白1（LAT1）的不同表达，色氨酸的主要转运蛋白,和暴露于抑制剂（2-氨基-2-降冰片羧酸（BCH），L-亮氨酸）导致唾液侧的色氨酸水平增加。此外,在平衡研究中暴露于色氨酸导致LAT1在mRNA水平上的调节。这项研究中收集的数据表明，色氨酸通过口腔粘膜上皮的主动转运机制参与。未来的研究应该研究色氨酸在唾液腺上皮中的转运，以便全面了解血唾液屏障上的色氨酸交换。
