Based on the fact that human bile and, particularly gallbladder bile, contains high physiological levels of the antioxidant melatonin, the aim of this study was to investigate whether the melatonin receptor MT1 is present in human gallbladder. Expression and localization of MT1 was assessed by RT-PCR, Western blotting and immunofluorescence analysis in gallbladder samples from patients with cholelithiasis and with advanced gallbladder carcinoma. Additionally, we monitored mRNA expression of the two key enzymes of melatonin synthesis, i.e. arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT). MT1 mRNA and protein were present in all cholelithiasis (n = 10) and gallbladder carcinoma (n = 5) samples. As indicated from RT-PCR and Western blot studies, MT1 is located in gallbladder epithelia. Epithelial expression was further proven by immunofluorescence staining of MT1 in paraffin-embedded cholelithiasis and gallbladder carcinoma sections. Analysis of AANAT and HIOMT mRNA expression showed that HIOMT mRNA is present in gallbladder. Surprisingly, AANAT was not detectable under conditions where it was found in a human colon specimen. The absence of AANAT suggests that in human gallbladder, HIOMT might be involved in the formation of 5-hydroxytryptamine products other than melatonin. In summary, our results provide the first evidence for the presence of MT1 in human gallbladder epithelia. Therefore, in addition to its profound antioxidative effects in the biliary system, melatonin might also act through MT1-mediated signal transduction pathways. Thereby, it might be involved in the regulation of gallbladder function.

中文翻译：

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褪黑素受体亚型MT1在人胆囊上皮细胞中表达。

基于人类胆汁，尤其是胆囊胆汁含有高生理水平的抗氧化剂褪黑激素这一事实，本研究的目的是研究人类胆囊中是否存在褪黑激素受体MT1。通过RT-PCR，Western印迹和免疫荧光分析评估了胆结石病和晚期胆囊癌患者胆囊样品中MT1的表达和定位。此外，我们监测了褪黑激素合成的两个关键酶的mRNA表达，即芳基烷基胺-N-乙酰基转移酶（AANAT）和羟基吲哚-O-甲基转移酶（HIOMT）。MT1 mRNA和蛋白存在于所有胆石症（n = 10）和胆囊癌（n = 5）样本中。如RT-PCR和Western blot研究所示，MT1位于胆囊上皮细胞中。在石蜡包埋的胆石症和胆囊癌切片中MT1的免疫荧光染色进一步证实了上皮表达。对AANAT和HIOMT mRNA表达的分析表明，胆囊中存在HIOMT mRNA。令人惊讶的是，在人类结肠标本中发现AANAT的条件下无法检测到。AANAT的缺乏表明在人类胆囊中，HIOMT可能参与了褪黑激素以外的5-羟色胺产品的形成。总而言之，我们的结果为人类胆囊上皮细胞中MT1的存在提供了第一个证据。因此，褪黑激素除了在胆道系统中具有深远的抗氧化作用外，还可能通过MT1介导的信号转导途径起作用。因此，它可能参与胆囊功能的调节。