Fig 1.
Normalized gastropancreatic gene expression data (log2) for key enzymes in tryptophan serotonin and melatonin metabolism and receptors for melatonin and serotonin.
a) Human small intestinal epithelium (GSE9576) b) Human pancreas (GSE15471) c) Human pancreas (GSE16515) d) Human pancreatic islets (GSE38642). MT2 expression levels exceed MT1 levels in small intestine, whole pancreas and islets. (* p<0.05, *** p<0.001, **** p<0.0001).
Table 1.
Data from GEO series GSE11223 was analyzed using the limma R package on GEO2R in order to find differentially expressed genes between colon biopsies from UC patients (inflamed) and healthy controls (not inflamed).
Fig 2.
Immunohistochemical staining of gastrointestinal tract and pancreas tissue with antibodies against melatonin and receptors MT1 and MT2.
A) Strong MT1 receptor immunoreactivity (IR) in epithelium in pyloric mucosa. B) Strong MT2 receptor IR in epithelium and endocrine cell (arrow) in pyloric mucosa. C) Weak MT1 receptor IR in epithelium in ileal mucosa. D) MT2 receptor IR is negative in epithelial cells but strong in endocrine cells (arrow) in duodenal mucosa E) Strong MT1 receptor IR in epithelium of colon mucosa. Insert shows neutralization test for MT1. F) Strong MT2 receptor IR in epithelium and endocrine cells (arrow) in colon mucosa. Insert shows neutralization test for MT2. G) Strong melatonin IR in endocrine cells in pyloric mucosa. H) Strong melatonin IR in endocrine cells in ileal mucosa. I) Strong melatonin IR in epithelial cells and endocrine cells in colon mucosa. Insert shows neutralization test for melatonin. A-I: Magnification 100X. J) Strong melatonin IR in endocrine cells in pancreatic islets. Inset shows negative serotonin IR. K) Strong MT1 receptor IR in endocrine cells in pancreatic islets. L) Strong MT2 receptor IR in endocrine cells in pancreatic islets and pancreatic ducts. (J-K: Magnification 200X).
Fig 3.
Immunohistochemical staining of melatonin receptors in specific cell types.
A) Positive melatonin receptor 1 (MT1) immunoreactivity (IR) in epithelial cells. B) Melatonin receptor 2 (MT2) IR in epithelial cells. C) Arrow indicates negative MT1 IR in the submucosal plexus. D) Arrow indicates positive MT2 IR in the submucosal plexus. E) Arrow indicates a cell showing positive MT1 IR in the myenteric plexus; muscle cells are negative. F) Large arrow indicates positive MT2 IR in the myenteric plexus, small arrow indicates positive IR in muscle tissue. G) Large arrow indicates weak MT1 IR in the endothelium of arterioles and venules. H) Large arrow indicates MT2 IR in the endothelium and smooth muscle of arterioles and venules. Magnification 200X.
Table 2.
Localization of melatonin (Mel) and receptors (MT1 and MT2) in human gastrointestinal tract and pancreas assessed using immunohistochemistry.
Fig 4.
Confocal images of double immunofluorescence staining of crypts of Lieberkühn in ileum mucosa.
A: Melatonin immunoreactive (IR) cells. B: Serotonin IR cells. C: Merge A-C; Inset: magnification of cell in circle. Arrow indicates structures positive for serotonin but not melatonin. Square indicates cell where melatonin IR is strong compared to serotonin IR. D: Melatonin receptor MT1 IR in crypt epithelium. E: Serotonin IR cell. F: Merge D-F; Arrow indicates serotonin IR cell negative for melatonin receptor MT1. G: Melatonin receptor MT2 IR. H: Serotonin IR cells. I: Merge GI: Arrow indicates serotonin IR cell positive for melatonin receptor MT2. White bar indicates 20 μm.