Distribution of serotonin-immunoreactive nerve cells and fibers in the rat gastrointestinal tract

Fujimiya, Mineko; Okumiya, Kiyohito; Yamane, Tetsunobu; Maeda, Toshihiro

doi:10.1007/s004180050094

Cited by 36 publications

(33 citation statements)

References 23 publications

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“…For the detection of insulin-or proinsulin-positive cells, we fixed 20-m-thick frozen sections or 5-m-thick paraffin sections and processed them for immunohistochemical staining by using the avidin-biotin peroxidase complex (ABC) method and diaminobenzidine (DAB)-nickel reactions as described (13,15). Briefly, for insulin or proinsulin staining, frozen sections were incubated for 2 days with antibody against insulin (guinea pig polyclonal, Linco Research, St. Charles, MO) or proinsulin (guinea pig polyclonal, Progen, Heidelberg) diluted 1:5,000 in 0.1% PBS containing 0.3% Triton X-100 (PBST) at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Extrapancreatic insulin-producing cells in multiple organs in diabetes

Kojima

Fujimiya

Matsumura

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

183

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Insulin-producing cells normally occur only in the pancreas and thymus. Surprisingly, we found widespread insulin mRNA and protein expression in different diabetic mouse and rat models, including streptozotocin-treated mice and rats, ob͞ob mice, and mice fed high-fat diets. We detected in diabetic mice proinsulinand insulin-positive cells in the liver, adipose tissue, spleen, bone marrow, and thymus; many cells also produced glucagon, somatostatin, and pancreatic polypeptide. By in situ nucleic acid hybridization, diabetic, but not nondiabetic, mouse liver exhibited insulin transcript-positive cells, indicating that insulin was synthesized by these cells. In transgenic mice that express GFP driven by the mouse insulin promoter, streptozotocin-induced diabetes led to the appearance of GFP-positive cells in liver, adipose tissue, and bone marrow; the fluorescent signals showed complete concordance with the presence of immunoreactive proinsulin. Hyperglycemia produced by glucose injections in nondiabetic mice led to the appearance of proinsulin-and insulin-positive cells within 3 days. Bone marrow transplantation experiments showed that most of the extrapancreatic proinsulin-producing cells originated from the bone marrow. Immunoreactive proinsulin-and insulin-positive cells were also detected in the liver, adipose tissue, and bone marrow of diabetic rats, indicating that extrapancreatic, extrathymic insulin production occurs in more than one species. These observations have implications for the regulation of insulin gene expression, modulation of selftolerance by insulin gene expression, and strategies for the generation of insulin-producing cells for the treatment of diabetes.pancreatic islets ͉ hyperglycemia ͉ ob͞ob ͉ obesity ͉ bone marrow transplantation I nsulin is normally produced in highly specialized cells of the endocrine pancreas. The tissue-specific expression of insulin is tightly regulated at the transcriptional level, and the major regulatory elements are located in the 5Ј flanking region of the insulin gene (1). Insulin expression is specific to ␤ cells in the pancreatic islets, although proinsulin has also been detected in the fetal and postnatal thymus and spleen͞lymphoid tissues (2, 3), a pattern of promiscuous expression of normally tissuerestricted ''peripheral'' proteins in these tissues (4, 5). Immunoreactivity to insulin plays a key role in autoimmune diabetes in NOD mice (6, 7) and in type 1 diabetes in humans (7); expression of minute amounts of insulin in the thymus is believed to be important in the induction of tolerance to insulin and other ''self-antigens '' (8-11). In this study, we found insulin gene transcription and protein expression in multiple tissues outside the pancreas and thymus in mice and rats with diabetes. The widespread occurrence of extrapancreatic, extrathymic insulin gene products in diabetic animals is surprising; it suggests that we should revise our thinking on the regulation of insulin gene expression, the mechanism of immune tolerance to insulin, the pathophysi...

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Section: Methodsmentioning

confidence: 99%

Extrapancreatic insulin-producing cells in multiple organs in diabetes

Kojima

Fujimiya

Matsumura

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

183

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“…For instance, 5-HT is known to be present in pulmonary tissues where the source may be pulmonary neuroendocrine cells (50,51) or platelets (52), and thus could facilitate MC accumulation in inflammatory conditions of the lung. Similarly, 5-HT is known to be synthesized by enterochromaffin cells and nerve ganglia in the gastrointestinal system (53)(54)(55), and might influence accumulation of MC at these sites. In summary, we, for the first time, have shown that 5-HT has the ability to influence the biology of the MC.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine Induces Mast Cell Adhesion and Migration

Kushnir-Sukhov

Gilfillan

Coleman

et al. 2006

The Journal of Immunology

132

109

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The neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) is implicated in enhancing inflammatory reactions of skin, lung, and gastrointestinal tract. To determine whether 5-HT acts, in part, through mast cells (MC), we first established that mouse bone marrow-derived MC (mBMMC) and human CD34+-derived MC (huMC) expressed mRNA for multiple 5-HT receptors. We next determined the effect of 5-HT on mouse and human MC degranulation, adhesion, and chemotaxis. We found no evidence that 5-HT degranulates MC or modulates IgE-dependent activation. 5-HT did induce mBMMC and huMC adherence to fibronectin; and immature and mature mBMMC and huMC migration. Chemotaxis was accompanied by actin polymerization. Using receptor antagonists and pertussis toxin, we identified 5-HT1A as the principal receptor mediating the effects of 5-HT on MC. mBMMC from the 5-HT1A receptor knockout mouse (5-HT1AR−/−) did not respond to 5-HT. 5-HT did induce accumulation of MC in the dermis of 5-HT1AR+/+ mice, but not in 5-HT1AR−/− mice. These studies are the first to demonstrate an effect of 5-HT on MC. Furthermore, both mouse and human MC respond to 5-HT through the 5-HT1A receptor. Our data are consistent with the conclusion that 5-HT promotes inflammation by increasing MC at the site of tissue injury.

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“…Immunohistochemical investigations confirmed that the majority of serotonin exists in enterochromaffin cells [11, 12]. Serotoninergic neurons in the submucosal layer may contribute to the synthesis of peripheral serotonin as well [13]. Using homogenized tissue extracts from certain regions of the mouse duodenal mucosa, the major enzyme activity of the tryptophan hydroxylase was found to reside between the upper villus region and the bottom of the crypts [9].…”

Section: Introductionmentioning

confidence: 94%

“…Using homogenized tissue extracts from certain regions of the mouse duodenal mucosa, the major enzyme activity of the tryptophan hydroxylase was found to reside between the upper villus region and the bottom of the crypts [9]. This finding had led to the hypothesis that the expression of tryptophan hydroxylase is restricted either to enterochromaffin cells scattered in the mucosal epithelium or to serotoninergic neurons of the nerve plexuses [9, 13, 14]. However, the exact cellular distribution of tryptophan hydroxylase in the gastrointestinal tract has not been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Differential Distribution of Serotonin and Tryptophan Hydroxylase in the Human Gastrointestinal Tract

Meyer

Brinck²

1999

Digestion

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The distribution of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, was investigated immunohistochemically in various organs of the gastrointestinal tract and compared with that of neuroendocrine markers. While immunoreactivity for serotonin and chromogranin A was restricted to enterochromaffin cells, positive staining for tryptophan hydroxylase was detected in normal enterocytes lining the epithelium of the small intestine. Tryptophan hydroxylase was localized in the supranuclear cytoplasm of absorptive cells, and was absent from the terminal web. The enterocytes of the exfoliation zone at the tips of the villi demonstrated a strong immunoreactivity similar to those at the slope of the villi. Mucus-containing Goblet cells, Paneth cells and stromal cells of the lamina propria remained unlabelled. The duodenal glands of Brunner revealed only sporadically a weak immunostaining for tryptophan hydroxylase. The monooxygenase was also detected in numerous secretory tubules of the pyloric mucosa, where the proportion of positive cells decreased progressively from the crypts towards the upper parts of the gastric glands. No significant immunoreactivity was demonstrated in colon, adrenal cortex, liver, pancreas, and mesenteric lymph nodes. The demonstration of tryptophan hydroxylase in normal enterocytes suggested that epithelial cells of the small intestine are able to synthesize 5-hydroxytryptophan.

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Distribution of serotonin-immunoreactive nerve cells and fibers in the rat gastrointestinal tract

Cited by 36 publications

References 23 publications

Extrapancreatic insulin-producing cells in multiple organs in diabetes

Extrapancreatic insulin-producing cells in multiple organs in diabetes

5-Hydroxytryptamine Induces Mast Cell Adhesion and Migration

Differential Distribution of Serotonin and Tryptophan Hydroxylase in the Human Gastrointestinal Tract

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