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PubMed Central (PMC3 - NLM DTD) (2,796,061 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).

American Journal of Physiology - Gastrointestinal and Liver Physiology

Mostrando recursos 121 - 140 de 843

121. Keratinocyte growth factor-2 stimulates P-glycoprotein expression and function in intestinal epithelial cells - Saksena, Seema; Priyamvada, Shubha; Kumar, Anoop; Akhtar, Maria; Soni, Vikas; Anbazhagan, Arivarasu Natarajan; Alakkam, Anas; Alrefai, Waddah A.; Dudeja, Pradeep K.; Gill, Ravinder K.
Intestinal P-glycoprotein (Pgp/multidrug resistance 1), encoded by the ATP-binding cassette B1 gene, is primarily involved in the transepithelial efflux of toxic metabolites and xenobiotics from the mucosa into the gut lumen. Reduced Pgp function and expression has been shown to be associated with intestinal inflammatory disorders. Keratinocyte growth factor-2 (KGF2) has emerged as a potential target for modulation of intestinal inflammation and maintenance of gut mucosal integrity. Whether KGF2 directly regulates Pgp in the human intestine is not known. Therefore, the present studies were undertaken to determine the modulation of Pgp by KGF2 using Caco-2 cells. Short-term treatment of Caco-2...

122. Physiology of esophageal sensorimotor malfunctions in neonatal neurological illness - Jadcherla, Sudarshan R.; Chan, Chin Yee; Moore, Rebecca; Fernandez, Soledad; Shaker, Reza
We aimed to define the sensorimotor characteristics of aero-digestive reflexes evoked upon midesophageal provocations in neuropathology infants. Provocative esophageal motility testing was performed in 20 neuropathology infants and 10 controls at 42.3 ± 0.6 and 38.9 ± 0.9 wk postmenstrual age. Data from 1,073 infusions were examined for the sensory thresholds, response frequencies, response magnitude of upper esophageal sphincter (UES) contractile reflexes, lower esophageal sphincter (LES) relaxation reflexes, and peristaltic reflexes using mixed statistical models. Threshold volumes for air and liquid in neuropathology and control infants were similar for all reflexes. Graded air- and liquid volume-dependent UES contractile reflex, LES...

123. p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways - Huynh, Nhi; Yim, Mildred; Chernoff, Jonathan; Shulkes, Arthur; Baldwin, Graham S.; He, Hong
Gastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and...

124. Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment - Lalor, Patricia F.; Herbert, John; Bicknell, Roy; Adams, David H.
Platelets have recently been shown to drive liver injury in murine models of viral hepatitis and promote liver regeneration through the release of serotonin. Despite their emerging role in inflammatory liver disease, little is known about the mechanisms by which platelets bind to the hepatic vasculature. Therefore, we referenced public expression data to determine the profile of potential adhesive receptors expressed by hepatic endothelium. We then used a combination of tissue-binding and flow-based endothelial-binding adhesion assays to show that resting platelets bind to human hepatic sinusoidal endothelial cells and that the magnitude of adhesion is greatly enhanced by thrombin-induced platelet...

125. Anatomical and functional characterization of a duodeno-pancreatic neural reflex that can induce acute pancreatitis - Li, Cuiping; Zhu, Yaohui; Shenoy, Mohan; Pai, Reetesh; Liu, Liansheng; Pasricha, Pankaj Jay
Neural cross talk between visceral organs may play a role in mediating inflammation and pain remote from the site of the insult. We hypothesized such a cross talk exists between the duodenum and pancreas, and further it induces pancreatitis in response to intraduodenal toxins. A dichotomous spinal innervation serving both the duodenum and pancreas was examined, and splanchnic nerve responses to mechanical stimulation of these organs were detected. This pathway was then excited on the duodenal side by exposure to ethanol followed by luminal mustard oil to activate transient receptor potential subfamily A, member 1 (TRPA1). Ninety minutes later, pancreatic...

126. Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway - Rajagopal, Senthilkumar; Kumar, Divya P.; Mahavadi, Sunila; Bhattacharya, Sayak; Zhou, Ruizhe; Corvera, Carlos U.; Bunnett, Nigel W.; Grider, John R.; Murthy, Karnam S.
The present study characterized the TGR5 expression and the signaling pathways coupled to this receptor that mediates the relaxation of gastric smooth muscle. TGR5 was detected in gastric muscle cells by RT-PCR and Western blotting. Treatment of cells with the TGR5-selective ligand oleanolic acid (OA) activated Gαs, but not Gαq, Gαi1, Gαi2, or Gαi3, and increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol-induced contraction of gastric muscle cells from wild-type mice, but not tgr5−/− mice. OA, but not a selective exchange protein activated by cAMP (Epac) ligand (8-pCPT-2′-O-Me-cAMP), caused phosphorylation of RhoA and the phosphorylation...

127. Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism - Groschwitz, Katherine R.; Wu, David; Osterfeld, Heather; Ahrens, Richard; Hogan, Simon P.
Mast cells regulate intestinal barrier function during disease and homeostasis. Secretion of the mast cell-specific serine protease chymase regulates homeostasis. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial (Caco-2 BBe) cell monolayers induced a significant reduction in transepithelial resistance, indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Consistent with this observation, in vitro analysis revealed chymase-induced PAR-2 activation and increased MAPK activity...

128. Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells - Niederlechner, Stefanie; Baird, Christine; Petrie, Benjamin; Wischmeyer, Erhard; Wischmeyer, Paul E.
Epidermal growth factor receptor (EGFR) expression and signaling can induce cellular protection after intestinal inflammation. l-Glutamine (GLN) is known to prevent apoptosis after intestinal injury by activating MAPK and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. However, the role of EGFR expression and signaling in GLN-mediated cellular protection in intestinal epithelial-6 (IEC-6) cells after heat stress (HS) is unknown. To address the role of EGFR in GLN-mediated protection, IEC-6 cells were treated with GLN in the presence or absence of EGFR small interfering RNA, the EGFR tyrosine kinase inhibitor AG1478, the ERK1/2 inhibitor PD98059, the p38MAPK inhibitor SB203580, or the PI3-K/Akt inhibitor LY294002...

129. Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis - Michael, E. S.; Kuliopulos, A.; Covic, L.; Steer, M. L.; Perides, G.
Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2−/− mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca2+ concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury...

130. Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits - Camilleri, Michael; Kolar, Gururaj J.; Vazquez-Roque, Maria I.; Carlson, Paula; Burton, Duane D.; Zinsmeister, Alan R.
Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by χ2 test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model....

131. Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice - Potthoff, Matthew J.; Potts, Austin; He, Tianteng; Duarte, João A. G.; Taussig, Ronald; Mangelsdorf, David J.; Kliewer, Steven A.; Burgess, Shawn C.
Bile acid sequestrants are nonabsorbable resins designed to treat hypercholesterolemia by preventing ileal uptake of bile acids, thus increasing catabolism of cholesterol into bile acids. However, sequestrants also improve hyperglycemia and hyperinsulinemia through less characterized metabolic and molecular mechanisms. Here, we demonstrate that the bile acid sequestrant, colesevelam, significantly reduced hepatic glucose production by suppressing hepatic glycogenolysis in diet-induced obese mice and that this was partially mediated by activation of the G protein-coupled bile acid receptor TGR5 and glucagon-like peptide-1 (GLP-1) release. A GLP-1 receptor antagonist blocked suppression of hepatic glycogenolysis and blunted but did not eliminate the effect of...

132. Evidence of functional cross talk between the Notch and NF-κB pathways in nonneoplastic hyperproliferating colonic epithelium - Ahmed, Ishfaq; Roy, Badal; Chandrakesan, Parthasarathy; Venugopal, Anand; Xia, Lijun; Jensen, Roy; Anant, Shrikant; Umar, Shahid
The Notch and NF-κB signaling pathways regulate stem cell function and inflammation in the gut, respectively. We investigate whether a functional cross talk exists between the two pathways during transmissible murine colonic hyperplasia (TMCH) caused by Citrobacter rodentium (CR). During TMCH, NF-κB activity and subunit phosphorylation in colonic crypts of NIH Swiss mice at days 6 and 12 were associated with increases in downstream target CXC chemokine ligand (CXCL)-1/keratinocyte-derived chemokine (KC) expression. Blocking Notch signaling acutely for 5 days with the Notch blocker dibenzazepine (DBZ) failed to inhibit crypt NF-κB activity or CXCL-1/KC expression. Chronic DBZ administration for 10 days,...

133. Cell culture retains contractile phenotype but epigenetically modulates cell-signaling proteins of excitation-contraction coupling in colon smooth muscle cells - Shi, Xuan-Zheng; Sarna, Sushil K.
Smooth muscle cell cultures are used frequently to investigate the cellular mechanisms of contraction. We tested the hypothesis that cell culture alters the expression of select cell-signaling proteins of excitation-contraction coupling in colon smooth muscle cells without altering the contractile phenotype. We used muscularis externa (ME) tissues, freshly dispersed cells (FC), primary cell cultures (PC), and resuspensions of cell cultures (RC). Colon smooth muscle cells retained their phenotype in all states. We investigated expression of 10 cell-signaling proteins of excitation-contraction coupling in all four types of tissue. Expression of all these proteins did not differ between ME and FC (P...

134. Expression of bile acid receptor TGR5 in gastric adenocarcinoma - Cao, Weibiao; Tian, Wei; Hong, Jie; Li, Dan; Tavares, Rosemarie; Noble, Lelia; Moss, Steven F.; Resnick, Murray B.
Bile reflux is a risk factor in the development of intestinal metaplasia in the stomach and is believed to function as an initiator of gastric carcinogenesis. However, whether the G protein-coupled bile acid receptor TGR5 is expressed in this tumor is not known. In this study, we determined the expression of TGR5 in gastric adenocarcinoma and examined the role of TGR5 in cell proliferation. Strong TGR5 staining was present in 12% of cases of intestinal metaplasia but in no cases of normal gastric epithelium (P < 0.01). Moderate to strong TGR5 membranous and cytoplasmic staining was present in 52% of...

135. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent - Yang, Zhonghan; Sun, Rex; Grinchuk, Viktoriya; Blanco, Joan Antoni Fernandez; Notari, Luigi; Bohl, Jennifer A.; McLean, Leon P.; Ramalingam, Thirumalai R.; Wynn, Thomas A.; Urban, Joseph F.; Vogel, Stefanie N.; Shea-Donohue, Terez; Zhao, Aiping
IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical “type 2” immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected...

136. Modulation of the gut microbiota with antibiotic treatment suppresses whole body urea production in neonatal pigs - Puiman, Patrycja; Stoll, Barbara; Mølbak, Lars; de Bruijn, Adrianus; Schierbeek, Henk; Boye, Mette; Boehm, Günther; Renes, Ingrid; van Goudoever, Johannes; Burrin, Douglas
We examined whether changes in the gut microbiota induced by clinically relevant interventions would impact the bioavailability of dietary amino acids in neonates. We tested the hypothesis that modulation of the gut microbiota in neonatal pigs receiving no treatment (control), intravenously administered antibiotics, or probiotics affects whole body nitrogen and amino acid turnover. We quantified whole body urea kinetics, threonine fluxes, and threonine disposal into protein, oxidation, and tissue protein synthesis with stable isotope techniques. Compared with controls, antibiotics reduced the number and diversity of bacterial species in the distal small intestine (SI) and colon. Antibiotics decreased plasma urea concentrations...

137. NHE8 plays important roles in gastric mucosal protection - Xu, Hua; Li, Jing; Chen, Huacong; Wang, Chunhui; Ghishan, Fayez K.
Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the...

138. Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes - Petrescu, Anca D.; Huang, Huan; Martin, Gregory G.; McIntosh, Avery L.; Storey, Stephen M.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm
Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-α (PPARα) transcription of proteins involved in long-chain fatty acid (LCFA) β-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPARα-null mice with these major findings: 1) PUFA-mediated increase in the expression of PPARα-regulated LCFA β-oxidative enzymes, LCFA/LCFA-CoA binding proteins (L-FABP, ACBP), and PPARα itself was L-FABP dependent; 2) PPARα transcription, robustly potentiated by high glucose but not maltose, a sugar...

139. Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion - Daly, Kristian; Al-Rammahi, Miran; Moran, Andrew; Marcello, Marco; Ninomiya, Yuzo; Shirazi-Beechey, Soraya P.
CCK is secreted by endocrine cells of the proximal intestine in response to dietary components, including amino acids. CCK plays a variety of roles in digestive processes, including inhibition of food intake, consistent with a role in satiety. In the lingual epithelium, the sensing of a broad spectrum of l-amino acids is accomplished by the heteromeric amino acid (umami) taste receptor (T1R1-T1R3). T1R1 and T1R3 subunits are also expressed in the intestine. A defining characteristic of umami sensing by T1R1-T1R3 is its potentiation by IMP or GMP. Furthermore, T1R1-T1R3 is not activated by Trp. We show here that, in response...

140. d-Glucose modulates intestinal Niemann-Pick C1-like 1 (NPC1L1) gene expression via transcriptional regulation - Malhotra, Pooja; Boddy, Craig S.; Soni, Vinay; Saksena, Seema; Dudeja, Pradeep K.; Gill, Ravinder K.; Alrefai, Waddah A.
The expression of intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter has been shown to be elevated in patients with diseases associated with hypercholesterolemia such as diabetes mellitus. High levels of glucose were shown to directly increase the expression of NPC1L1 in intestinal epithelial cells, but the underlying mechanisms are not fully defined. The present studies were, therefore, undertaken to examine the transcriptional regulation of NPC1L1 expression in human intestinal Caco2 cells in response to glucose. Removal of glucose from the culture medium of Caco2 cells for 24 h significantly decreased the NPC1L1 mRNA, protein expression, as well as the promoter...

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