title: The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia.
abstract: 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.
authors.affiliation: Department of Pathophysiology, University of Vienna, Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Aust
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
authors.forename: Susanne
authors.initials: S
authors.lastname: Humpeler
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Martin
authors.initials: M
authors.lastname: Klimpfinger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Tucek
authors.forename: Peter
authors.initials: P
authors.lastname: Obrist
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Marktl
authors.forename: Edward
authors.initials: E
authors.lastname: Penner
authors.forename: Cem
authors.initials: C
authors.lastname: Ekmekcioglu
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D047068:Arylalkylamine N-Acetyltransferase; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002769:Cholelithiasis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005704:Gallbladder / Q000166:cytology / Q000378:metabolism*; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D000121:Acetylserotonin O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; C478879:AANAT protein, human; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin