scholarly journals Molecular mechanisms of calcium signaling in the modulation of small intestinal ion transports and bicarbonate secretion

Oncotarget ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 3727-3740 ◽  
Author(s):  
Xin Yang ◽  
Guorong Wen ◽  
Biguang Tuo ◽  
Fenglian Zhang ◽  
Hanxing Wan ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Molecular Mechanisms ◽  
Bicarbonate Secretion ◽  
Small Intestinal

scholarly journals FFA2 activation combined with ulcerogenic COX inhibition induces duodenal mucosal injury via the 5-HT pathway in rats

2017 ◽  
Vol 313 (2) ◽  
pp. G117-G128 ◽  
Author(s):  
Yasutada Akiba ◽  
Koji Maruta ◽  
Kazuyuki Narimatsu ◽  
Hyder Said ◽  
Izumi Kaji ◽  
...  
Keyword(s):  
Blood Flow ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Serotonin Release ◽  
Enterochromaffin Cells ◽  
Bicarbonate Secretion ◽  
Rat Duodenum ◽  
Free Fatty Acid Receptor ◽  
Small Intestinal

Serotonin (5-HT), predominantly synthesized and released by enterochromaffin cells, is implicated in gastrointestinal symptoms such as emesis, abdominal pain, and diarrhea. Because luminal short-chain fatty acids (SCFAs) release 5-HT from enterochromaffin cells, which express the SCFA receptor free fatty acid receptor 2 (FFA2) in rat duodenum, we examined the effects of the selective FFA2 agonist phenylacetamide-1 (PA1) on duodenal 5-HT release with consequent bicarbonate secretion [duodenal bicarbonate secretion (DBS)] and on indomethacin (IND)-induced enteropathy. Intestinal injury was induced by IND (10 mg/kg sc) with or without PA1. We measured DBS in vivo in a duodenal loop perfused with PA1 while measuring 5-HT released in the portal vein. Duodenal blood flow was measured by laser-Doppler flowmetry. IND induced small intestinal ulcers with duodenal sparing. PA1 given with IND (IND + PA1) dose dependently induced duodenal erosions. IND + PA1-induced duodenal lesions were inhibited by the FFA2 antagonist GLPG-0974, ondansetron, or omeprazole but not by RS-23597 or atropine. Luminal perfusion of PA1 augmented DBS accompanied by increased portal blood 5-HT concentrations with approximately eight times more release at 0.1 mM than at 1 µM, with the effects inhibited by coperfusion of GLPG-0974. Luminal PA1 at 1 µM increased, but at 0.1 mM diminished, duodenal blood flow. Cosuperfusion of PA1 (0.1 mM) decreased acid-induced hyperemia, further reduced by IND pretreatment but restored by ondansetron. These results suggest that, although FFA2 activation enhances duodenal mucosal defenses, FFA2 overactivation during ulcerogenic cyclooxygenase inhibition may increase the vulnerability of the duodenal mucosa to gastric acid via excessive 5-HT release and 5-HT3receptor activation, implicated in foregut-related symptoms such as emesis and epigastralgia.NEW & NOTEWORTHY Luminal free fatty acid receptor 2 agonists stimulate enterochromaffin cells and release serotonin, which enhances mucosal defenses in rat duodenum. However, overdriving serotonin release with high luminal concentrations of free fatty acid 2 ligands such as short-chain fatty acids injures the mucosa by decreasing mucosal blood flow. These results are likely implicated in serotonin-related dyspeptic symptom generation because of small intestinal bacterial overgrowth, which is hypothesized to generate excess SCFAs in the foregut, overdriving serotonin release from enterochromaffin cells.

scholarly journals Calcium signaling and molecular mechanisms underlying neurodegenerative diseases

Cell Calcium ◽  
2018 ◽  
Vol 70 ◽  
pp. 87-94 ◽  
Author(s):  
Ekaterina Pchitskaya ◽  
Elena Popugaeva ◽  
Ilya Bezprozvanny
Keyword(s):  
Neurodegenerative Diseases ◽  
Calcium Signaling ◽  
Molecular Mechanisms

scholarly journals Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xin-Jing Yang ◽  
Jin-Xian Qian ◽  
Yao Wei ◽  
Qiang Guo ◽  
Jun Jin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Injury ◽  
Beclin 1 ◽  
Tanshinone Iia ◽  
Inflammatory Factors ◽  
Rt Pcr ◽  
Intestinal Tissue ◽  
Sodium Sulfonate ◽  
Small Intestinal Injury ◽  
Small Intestinal

Background. Tanshinone IIA sodium sulfonate (TSS) is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS-) induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6) in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3) and Beclin-1) were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

scholarly journals Nutritional and Physiological Constraints Contributing to Limitations in Small Intestinal Starch Digestion and Glucose Absorption in Ruminants

Ruminants ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 1-26
Author(s):  
Ronald J. Trotta ◽  
David L. Harmon ◽  
James C. Matthews ◽  
Kendall C. Swanson
Keyword(s):  
Small Intestine ◽  
Molecular Mechanisms ◽  
Glucose Absorption ◽  
Feeding Strategies ◽  
Starch Digestion ◽  
Sucrase Activity ◽  
Physiological Constraints ◽  
Small Intestinal ◽  
Intestinal Sucrase ◽  
Intestinal Sucrase Activity

Increased efficiency of nutrient utilization can potentially be gained with increased starch digestion in the small intestine in ruminants. However, ruminants have quantitative limits in the extent of starch disappearance in the small intestine. The objective is to explore the nutritional and physiological constraints that contribute to limitations of carbohydrate assimilation in the ruminant small intestine. Altered digesta composition and passage rate in the small intestine, insufficient pancreatic α-amylase and/or small intestinal carbohydrase activity, and reduced glucose absorption could all be potentially limiting factors of intestinal starch assimilation. The absence of intestinal sucrase activity in ruminants may be related to quantitative limits in small intestinal starch hydrolysis. Multiple sequence alignment of the sucrase-isomaltase complex gives insight into potential molecular mechanisms that may be associated with the absence of intestinal sucrase activity, reduced capacity for intestinal starch digestion, and limitations in the efficiency of feed utilization in cattle and sheep. Future research efforts in these areas will aid in our understanding of small intestinal starch digestion and glucose absorption to optimize feeding strategies for increased meat and milk production efficiency.

scholarly journals Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes

2011 ◽  
Vol 300 (3) ◽  
pp. G425-G432 ◽  
Author(s):  
Lei Lu ◽  
Tiantian Li ◽  
Graham Williams ◽  
Elizabeth Petit ◽  
Mark Borowsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Molecular Mechanisms ◽  
Cell Maturation ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Tight Junction Formation ◽  
Expression Of Genes ◽  
Small Intestinal

It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC), including an increased expression of digestive hydrolases. However, the molecular mechanisms are not well understood, particularly in the human gut. Here we report a microarray analysis of HC-induced changes in gene expression in H4 cells (a well-characterized human fetal small intestinal epithelial cell line). This study identified a large number of HC-regulated genes, some involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication. HC also regulates the expression of genes important for cell maturation such as development of cell polarity, tight junction formation, and interactions with extracellular matrices. Using human small intestinal xenografts, we also show that HC can regulate the expression of genes important for intestinal epithelial cell maturation. Our dataset may serve as a useful resource for understanding and dissecting the molecular mechanisms of intestinal epithelial cell maturation.

Sign in / Sign up

Export Citation Format

Share Document