AJP: Gastrointestinal and Liver Physiology
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New method of manometric measurement of gastroduodenal motility in conscious mice: effects of ghrelin and Y2 depletion
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Since no previous studies have reported dual measurements of stomach and duodenal motility in conscious mice, we developed a manometric method to measure the gastroduodenal motility in the physiological fed and fasted states of conscious mice. By this method we measured, for the first time, the gastroduodenal motility in Y2 knockout mice and analyzed the effects of ghrelin on the gastroduodenal motility in conscious mice. To evaluate this new method, we provide the comparison on the effects of CCK-8 examined by present and previous methods. In the fasted state of mice, phase III-like contractions with frequencies of 7.8 &p...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Tanaka, R., Inui, A., Asakawa, A., Atsuchi, K., Ataka, K., Fujimiya, M. Tags: INNOVATIVE METHODOLOGY Source Type: journals
Angiotensin II receptors are expressed and functional in human esophageal mucosa
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In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT2-receptor stimulation increases epithelial ion transport, whereas the AT1 receptor inhibits ion transport and increases Rep. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Casselbrant, A., Edebo, A., Hallersund, P., Spak, E., Helander, H. F., Jonson, C., Fandriks, L. Tags: HORMONES AND SIGNALING Source Type: journals
Identification and functional characterization of the intermediate-conductance Ca2+-activated K+ channel (IK-1) in biliary epithelium
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In the liver, adenosine triphosphate (ATP) is an extracellular signaling molecule that is released into bile and stimulates a biliary epithelial cell secretory response via engagement of apical P2 receptors. The molecular identities of the ion channels involved in ATP-mediated secretory responses have not been fully identified. Intermediate-conductance Ca2+-activated K+ channels (IK) have been identified in biliary epithelium, but functional data are lacking. The aim of these studies therefore was to determine the location, function, and regulation of IK channels in biliary epithelial cells and to determine their potential...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Dutta, A. K., Khimji, A.-k., Sathe, M., Kresge, C., Parameswara, V., Esser, V., Rockey, D. C., Feranchak, A. P. Tags: LIVER AND BILIARY TRACT Source Type: journals
The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8
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Angiogenesis is required for wound healing and repair, but dysregulated angiogenesis is involved in gastrointestinal inflammation. Bacillus polyfermenticus (B.P.) is a probiotic bacterium clinically used for a variety of intestinal disorders in East Asia. Here we investigated the effect of B.P. on angiogenesis of human intestinal microvascular endothelial cells (HIMECs) and wound healing in intestinal mucosa. Exposure of HIMECs to the conditioned medium of B.P. cultures (B.P. CM) increased cell migration, permeability, and tube formation. Production of the proangiogenic cytokine IL-8 was increased by B.P. CM, and neutraliz...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Im, E., Choi, Y. J., Kim, C. H., Fiocchi, C., Pothoulakis, C., Rhee, S. H. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Protection from diclofenac-induced small intestinal injury by the JNK inhibitor SP600125 in a mouse model of NSAID-associated enteropathy
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In conclusion, these data demonstrate that the JNK pathway is critically involved in the pathogenesis of DCF-induced enteropathy and suggest a potential application of JNK inhibitors in the prevention of NSAID-induced enteropathy. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Ramirez-Alcantara, V., LoGuidice, A., Boelsterli, U. A. Tags: MUCOSAL BIOLOGY Source Type: journals
Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis
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The objective of this study was to investigate the role of MAPKAP kinase 2 (MK2) and heat shock protein (HSP) HSP60 in the pathogenesis of a new model of severe acute pancreatitis (AP). MK2 plays a significant role in the regulation of cytokines. It has been shown that induction and expression of several HSPs can protect against experimental pancreatitis. Interplay between both systems seems of high interest. Mice with a homozygous deletion of the MK2 gene were used. Severe AP was induced by combined intraperitoneal injections of cerulein with lipopolysaccharide (LPS). Severity of AP was assessed by biochemical markers and...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Li, Y.-Y., Ochs, S., Gao, Z.-R., Malo, A., Chen, C.-J., Lv, S., Gallmeier, E., Goke, B., Schafer, C. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Localization of acyl ghrelin- and des-acyl ghrelin-immunoreactive cells in the rat stomach and their responses to intragastric pH
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Acyl ghrelin has a 28-amino acid sequence with O-n-octanoyl acid modification at the serine 3 position, whereas des-acyl ghrelin has no octanoyl acid modification. Although these peptides exert different physiological functions, no previous studies have shown the different localization of acyl ghrelin and des-acyl ghrelin in the stomach. Here we have developed an antibody specific for des-acyl ghrelin that does not crossreact with acyl ghrelin. Both acyl ghrelin- and des-acyl ghrelin-immunoreactive cells were distributed in the oxyntic and antral mucosa of the rat stomach, with higher density in the antral mucosa than oxyn...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Mizutani, M., Atsuchi, K., Asakawa, A., Matsuda, N., Fujimura, M., Inui, A., Kato, I., Fujimiya, M. Tags: HORMONES AND SIGNALING Source Type: journals
Protease activation during in vivo pancreatitis is dependent on calcineurin activation
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In this study, we hypothesized that PP2B mediates in vivo protease activation and pancreatitis severity. To test this, pancreatitis was induced in mice over 8 h by administering hourly intraperitoneal injections of the cholecystokinin analog caerulein (50 µg/kg). Treatment with the PP2B inhibitor FK506 at 1 and 8 h after pancreatitis induction reduced trypsin activities by greater than 50% (P < 0.005). Serum amylase and IL-6 was reduced by 86 and 84% relative to baseline (P < 0.0005) at 8 h, respectively. Histological severity of pancreatitis, graded on the basis of pancreatic edema, acinar cell vacuolization, ...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Shah, A. U., Sarwar, A., Orabi, A. I., Gautam, S., Grant, W. M., Park, A. J., Shah, A. U., Liu, J., Mistry, P. K., Jain, D., Husain, S. Z. Tags: HORMONES AND SIGNALING Source Type: journals
Role of thin-filament regulatory proteins in relaxation of colonic smooth muscle contraction
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Coordinated regulation of smooth muscle contraction and relaxation is required for colonic motility. Contraction is associated with phosphorylation of myosin light chain (MLC20) and interaction of actin with myosin. Thin-filament regulation of actomyosin interaction is modulated by two actin-binding regulatory proteins: tropomyosin (TM) and caldesmon (CaD). TM and CaD are known to play crucial role in actomyosin interaction promoting contraction. Contraction is associated with phosphorylation of the small heat shock protein HSP27, concomitant with the phosphorylation of TM and CaD. Phosphorylation of HSP27 is attributed as...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Somara, S., Gilmont, R., Bitar, K. N. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport
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Roux-en-Y gastric bypass (RYGB) has become the gold-standard bariatric procedure, partly because of the rapid resolution of accompanying diabetes. There is increasing evidence this is mediated by duodenal exclusion. We hypothesize that duodenal exclusion suppresses intestinal Na+/glucose cotransporter SGLT1-mediated glucose transport, improving glucose handling, and aimed to test this in a rodent RYGB model. Sprague-Dawley rats underwent sham procedure or duodenal exclusion by RYGB (10 cm Roux, 16 cm biliopancreatic limbs). Animals were maintained for 3 wk on a Western diet, before harvest at 10 AM, 4 PM, and 10 PM. Sectio...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Stearns, A. T., Balakrishnan, A., Tavakkolizadeh, A. Tags: MUCOSAL BIOLOGY Source Type: journals
Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis
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In conclusion, administration of B. bifidum protects against NEC in the neonatal rat model. This protective effect is associated with reduction of inflammatory reaction in the ileum, regulation of main components of mucus layer, and improvement of intestinal integrity. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Khailova, L., Dvorak, K., Arganbright, K. M., Halpern, M. D., Kinouchi, T., Yajima, M., Dvorak, B. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Caveolin-1 mediates endotoxin inhibition of endothelin-1-induced endothelial nitric oxide synthase activity in liver sinusoidal endothelial cells
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The objective of this study was to investigate the molecular mechanism of Cav-1 in the regulation of LPS suppression of ET-1-mediated eNOS activation in LSECs by examining the effect of caveolae disruption using methyl-β-cyclodextrin (CD) and filipin. Treatment with 5 mM CD for 30 min increased eNOS activity (+255%, P < 0.05). A dose (0.25 µg/ml) of filipin for 30 min produced a similar effect (+111%, P < 0.05). CD induced the perinuclear localization of Cav-1 and eNOS and stimulated NO production in the same region. Readdition of 0.5 mM cholesterol to saturate CD reversed these effects. Both the combined ...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Kwok, W., Lee, S. H., Culberson, C., Korneszczuk, K., Clemens, M. G. Tags: LIVER AND BILIARY TRACT Source Type: journals
Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1
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The purpose of this investigation was to quantitate the contribution of the anion exchanger PAT-1 (putative anion transporter-1), encoded by SLC26A6, to oxalate transport in a model intestinal epithelium and to discern some characteristics of this exchanger expressed in its native environment. Control (Con) Caco-2 BBe1 monolayers, 6–8 days postseeding, were compared with those transfected with a small interfering RNA targeted to SLC26A6 (A6KD). Radiotracer and Ussing chamber techniques were used to determine the transepithelial unidirectional fluxes of Ox2–, Cl–, and SO42– whereas fluorometric/BCECF...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Freel, R. W., Morozumi, M., Hatch, M. Tags: MUCOSAL BIOLOGY Source Type: journals
Chronic oxidative stress sensitizes hepatocytes to death from 4-hydroxynonenal by JNK/c-Jun overactivation
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Sustained activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates the development and progression of experimental diet-induced nonalcoholic fatty liver disease (NAFLD). Delineating the mechanism of JNK overactivation in the setting of a fatty liver is therefore essential to understanding the pathophysiology of NAFLD. Both human and experimental NAFLD are associated with oxidative stress and resultant lipid peroxidation, which have been proposed to mediate the progression of this disease from simple steatosis to steatohepatitis. The ability of oxidants and the lipid peroxidation product 4-hydroxynonenal...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Singh, R., Wang, Y., Schattenberg, J. M., Xiang, Y., Czaja, M. J. Tags: LIVER AND BILIARY TRACT Source Type: journals
Contribution of different triggers to the gastric accommodation reflex in humans
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Accommodation of the stomach consists of a vagally mediated relaxation of the proximal stomach, providing the meal with a reservoir. Our aim was to study whether, similar to other vagally mediated processes, the accommodation reflex is also determined by cephalic, oropharyngeal, gastric, and intestinal phases. Eleven healthy subjects underwent in randomized order five gastric barostat studies and two satiety drinking tests. In all studies, isobaric tone measurements (at minimal distending pressure + 2 mmHg) were performed 20 min before and 20 min after a nutrient stimulus. The stimuli included only visual and olfactory exp...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Vanden Berghe, P., Janssen, P., Kindt, S., Vos, R., Tack, J. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI
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This study assessed the effects of meal volume (MV) and calorie load (CL) on gastric function. MRI and a minimally invasive fiber-optic recording system (FORS) provided simultaneous measurement of gastric volume and pressure changes during gastric filling and emptying of a liquid nutrient meal in physiological conditions. The gastric response to 12 iso-osmolar MV-CL combinations of a multinutrient drink (MV: 200, 400, 600, 800 ml; CL: 200, 300, 400 kcal) was tested in 16 healthy subjects according to a factorial design. Total gastric volume (TGV) and gastric content volume (GCV = MV + secretion) were measured by MRI during...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Kwiatek, M. A., Menne, D., Steingoetter, A., Goetze, O., Forras-Kaufman, Z., Kaufman, E., Fruehauf, H., Boesiger, P., Fried, M., Schwizer, W., Fox, M. R. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Effects of progesterone on motility and prostaglandin levels in the distal guinea pig colon
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Progesterone (P4) inhibits the gastrointestinal muscle contraction by downregulating Gq/11 proteins that mediate contraction, by upregulating Gs proteins that mediate relaxation, and by altering the pattern of cyclooxygenase (COX) enzymes and prostaglandins. We aimed to examine whether P4 treatment of guinea pigs in vivo affects basal colon motility [basal motility index (MI)] by altering the levels and actions of PGF2 and PGE2. Guinea pigs were treated with intramuscular (IM) P4 for 4 days. The BASAL MI, the PGF2-induced contraction, and PGE2-induced inhibition of contraction were examined in muscle strips and cells. The ...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Xiao, Z. L., Biancani, P., Behar, J. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Mechanisms underlying modulation of monocarboxylate transporter 1 (MCT1) by somatostatin in human intestinal epithelial cells
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Somatostatin (SST), an important neuropeptide of the gastrointestinal tract has been shown to stimulate sodium chloride absorption and inhibit chloride secretion in the intestine. However, the effects of SST on luminal butyrate absorption in the human intestine have not been investigated. Earlier studies from our group and others have shown that monocarboxylate transporter (MCT1) plays an important role in the transport of butyrate in the human intestine. The present studies were undertaken to examine the effects of SST on butyrate uptake utilizing postconfluent human intestinal epithelial Caco2 cells. Apical SST treatment...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Saksena, S., Theegala, S., Bansal, N., Gill, R. K., Tyagi, S., Alrefai, W. A., Ramaswamy, K., Dudeja, P. K. Tags: HORMONES AND SIGNALING Source Type: journals
Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?
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The relationship between a predisposition to obesity and the development of colitis is not well understood. Our aim was to characterize the adipokine response and the extent of colitis in diet-induced obese (DIO) rats. DIO and control, diet-resistant (DR) animals were administered either saline or trinitrobenzene sulfonic acid (TNBS) to induce colitis. Macroscopic damage scores and myeloperoxidase (MPO) activity were measured to determine the extent of inflammation. Trunk blood was collected for the analysis of plasminogen activator inhibitor-1 (PAI-1) as well as leptin, ghrelin, and adiponectin. Colonic epithelial physiol...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Hyland, N. P., Chambers, A. P., Keenan, C. M., Pittman, Q. J., Sharkey, K. A. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Mechanisms of gastric emptying disturbances in chronic and acute inflammation of the distal gastrointestinal tract
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It is unclear why patients with inflammation of the distal bowel complain of symptoms referable to the upper gastrointestinal tract, specifically to gastric emptying (GE) disturbances. Thus we aimed to determine occurrence and putative pathomechanisms of gastric motor disorders in such patients. Thirteen healthy subjects (CON), 13 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 7 with diverticulitis (DIV) underwent a standardized 13C-octanoic acid gastric emptying breath test. Plasma glucose, CCK, peptide YY, and glucagon-like peptide-1 (GLP-1) were measured periodically and correlated with GE para...
Source: AJP: Gastrointestinal and Liver Physiology - October 21, 2009 Category: Gastroenterology Authors: Keller, J., Beglinger, C., Holst, J. J., Andresen, V., Layer, P. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Retraction
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(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Tags: RETRACTION Source Type: journals
Shedding gloomy light into the black box of the Ussing chamber
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(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Lucas, M. L. Tags: LETTER TO THE EDITOR Source Type: journals
Alterations in mechanical properties of mesenteric resistance arteries in experimental portal hypertension
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Splanchnic vasodilation is the pathophysiological hallmark in the development of the hyperdynamic circulatory syndrome in liver cirrhosis and portal hypertension. This has been attributed so far mainly to a marked vascular hyporeactivity to endogenous vasoconstrictors. However, myogenic tone and vessel stiffness have not been addressed in mesenteric arteries in liver cirrhosis. CCl4–-induced ascitic cirrhotic (LC) and age-matched control rats, portal vein-ligated (PVL) rats, and sham-operated rats were investigated. Third-order mesenteric resistance arteries were studied under no-flow conditions using a pressure myog...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Resch, M., Wiest, R., Moleda, L., Fredersdorf, S., Stoelcker, B., Schroeder, J. A., Scholmerich, J., Endemann, D. H. Tags: LIVER AND BILIARY TRACT Source Type: journals
Extracellular activation of arginase-1 decreases enterocyte inducible nitric oxide synthase activity during systemic inflammation
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Liver dysfunction secondary to severe inflammation is associated with the release of enzymes normally sequestered within hepatocytes. The purpose of these studies was to test the hypothesis that these enzymes are released, at least in part, to modulate potentially deleterious inflammatory processes in distant tissues like the gut. Human Caco-2BBe enterocyte-like cells were exposed to cytomix (IFN-, TNF-, and IL-1β) in the absence or presence of human liver cytosol (LC). Nitric oxide (NO•) and inducible nitric oxide synthase (iNOS) protein production were measured by the Griess assay and Western analysis, respecti...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Miki, K., Kumar, A., Yang, R., Killeen, M. E., Delude, R. L. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Calcium-dependent and calcium-independent inhibition of contraction by cGMP/cGKI in intestinal smooth muscle
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cGMP-dependent protein kinase I (cGKI) induces relaxation of smooth muscle via several pathways that include inhibition of intracellular Ca2+ signaling and/or involve activation of myosin phosphatase. In the present study, we investigated these mechanisms comparatively in colon and jejunum longitudinal smooth muscle from mice. In simultaneous recordings from colon muscle, 8-bromo-cGMP (8-Br-cGMP) reduced both carbachol-induced tension and carbachol-induced increase in intracellular Ca2+ concentration ([Ca2+]i). These effects of 8-Br-cGMP were absent in colon from mice carrying a mutated inositol-1,4,5 trisphosphate recepto...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Frei, E., Huster, M., Smital, P., Schlossmann, J., Hofmann, F., Wegener, J. W. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Enteropathogenic Escherichia coli inhibits intestinal vitamin B1 (thiamin) uptake: studies with human-derived intestinal epithelial Caco-2 cells
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Infection with the gram-negative enteropathogenic Escherichia coli (EPEC), a food-borne pathogen, represents a significant risk to human health. Whereas diarrhea is a major consequence of this infection, malnutrition also occurs especially in severe and prolonged cases, which may aggravate the health status of the infected hosts. Here we examined the effect of EPEC infection on the intestinal uptake of the water-soluble vitamin B1 (thiamin) using an established human intestinal epithelial Caco-2 cell model. The results showed that infecting Caco-2 cells with wild-type EPEC (but not with nonpathogenic E. coli, killed EPEC, ...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Ashokkumar, B., Kumar, J. S., Hecht, G. A., Said, H. M. Tags: MUCOSAL BIOLOGY Source Type: journals
Interstitial cells of Cajal generate spontaneous transient depolarizations in the rat gastric fundus
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Intracellular recordings were made from isolated circular muscle bundles of rat gastric fundus. The majority of cells generated an ongoing discharge of electrical activity that were ≤10 mV in amplitude (unitary potentials). A second pattern of electrical activity was recorded in less than 1% of all impalements. This electrical activity was characterized by high frequency, large amplitude spontaneous transient depolarizations (STDs) with a maximum rate of rise (dV/dtmax) of 0.5 V/s. Injection of the fluorescent dye propidium iodide into cells and double labeling with an antibody against the Kit receptor revealed that uni...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Kito, Y., Sanders, K. M., Ward, S. M., Suzuki, H. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Role of PSD95 in membrane association and catalytic activity of nNOS{alpha} in nitrergic varicosities in mice gut
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We have recently shown that membrane association of neuronal nitric oxide synthase- (nNOS) is critical in the regulation of synthesis of NO during nitrergic neurotransmission. The purpose of this study was to examine the role of the synapse-associated proteins (SAPs) in membrane association of nNOS. Varicosities (swellings on terminal axons) were isolated from mice gastrointestinal tract and examined for nNOS, postsynaptic density protein 95 (PSD95), and membrane interactions by coimmunoprecipitation and SDS-PAGE. Our results show that PSD95 protein was present in the membrane fraction of the nerve varicosity, whereas both...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Chaudhury, A., He, X.-D., Goyal, R. K. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro
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Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of short-circuit current (Isc) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Baldassano, S., Liu, S., Qu, M.-H., Mule, F., Wood, J. D. Tags: HORMONES AND SIGNALING Source Type: journals
Role of endothelial nitric oxide synthase in the development of portal hypertension in the carbon tetrachloride-induced liver fibrosis model
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This study investigates the importance of eNOS and systemic hyperdynamic-associated hyperemia to better understand the pathophysiology of PHT. Wild-type and eNOS–/– mice were given the hepatotoxin CCl4 for 4–12 wk. Hepatic fibrosis was determined histologically following collagen staining. Portal venous pressure, hepatic resistance, and hyperemia were determined by measuring splenic pulp pressure (SPP), hepatic portal-venous perfusion pressure (HPVPP), abdominal aortic flow (Qao), and portal venous flow (Qpv). Hepatic fibrosis developed equally in wild-type and eNOS–/– CCl4-exposed mice. SPP, ...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Theodorakis, N. G., Wang, Y. N., Wu, J.-M., Maluccio, M. A., Sitzmann, J. V., Skill, N. J. Tags: LIVER AND BILIARY TRACT Source Type: journals
Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats
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Presence of taste receptor families in the gastrointestinal mucosa suggests a physiological basis for local and early detection of a meal. We hypothesized that luminal l-glutamate, which is the primary nutrient conferring fundamental umami or proteinaceous taste, influences mucosal defense mechanisms in rat duodenum. We perfused the duodenal mucosa of anesthetized rats with l-glutamate (0.1–10 mM). Intracellular pH (pHi) of the epithelial cells, blood flow, and mucus gel thickness (MGT) were simultaneously and continuously measured in vivo. Some rats were pretreated with indomethacin or capsaicin. Duodenal bicarbonat...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Akiba, Y., Watanabe, C., Mizumori, M., Kaunitz, J. D. Tags: MUCOSAL BIOLOGY Source Type: journals
Upregulation of activin signaling in experimental colitis
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Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a–/– mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while a...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Zhang, Y.-Q., Resta, S., Jung, B., Barrett, K. E., Sarvetnick, N. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Urotensin II modulates hepatic fibrosis and portal hemodynamic alterations in rats
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The influence of circulating urotensin II (UII) on liver disease and portal hypertension is unknown. We aimed to evaluate whether UII executes a pathogenetic role in the development of hepatic fibrosis and portal hypertension. UII was administered by continuous infusion over 4 wk in 20 healthy rats divided into three treatment groups, controls (saline, n = 7), low dose (UII, 1 nmol·kg–1·h–1, n = 8), and high dose (UII, 3 nmol·kg–1·h–1, n = 5). Hemodynamic parameters and morphometric quantification of fibrosis were assessed, and profibrotic cytokines and fibrosis markers w...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Kemp, W., Kompa, A., Phrommintikul, A., Herath, C., Zhiyuan, J., Angus, P., McLean, C., Roberts, S., Krum, H. Tags: LIVER AND BILIARY TRACT Source Type: journals
Mice lacking neurofibromin develop gastric hyperplasia
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In this study, we generated conditional knockout mice with Nf1 deficiency in the GI tract. These mice develop gastric epithelial hyperplasia and inflammation together with increased cell proliferation and apoptosis. The gastric phenotypes observed in these mutant mice seem to be the consequence of loss of Nf1 in gastric fibroblasts, resulting in paracrine hyperactivation of the ERK pathway in the gastric epithelium. These mice provide a useful model to study the pathogenesis of GI lesions in a subset of patients with NF1 and to investigate the role of the Nf1 gene in the development of GI neoplasms. (Source: AJP: Gastroint...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Lin, L., Chen, J., Richardson, J. A., Parada, L. F. Tags: HORMONES AND SIGNALING Source Type: journals
Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated with Citrobacter rodentium-induced colitis
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In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Conlin, V. S., Wu, X., Nguyen, C., Dai, C., Vallance, B. A., Buchan, A. M. J., Boyer, L., Jacobson, K. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: journals
Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C
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Angiotensin II promotes liver fibrogenesis by stimulating nonphagocytic NADPH oxidase (NOX)-induced oxidative stress. Angiotensin II type 1 (AT1) receptor blockers attenuate experimental liver fibrosis, yet their effects in human liver fibrosis are unknown. We investigated the effects of losartan on hepatic expression of fibrogenic, inflammatory, and NOX genes in patients with chronic hepatitis C (CHC). Fourteen patients with CHC and liver fibrosis received oral losartan (50 mg/day) for 18 mo. Liver biopsies were performed at baseline and after treatment. The degree of inflammation and fibrosis was evaluated by histologica...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Colmenero, J., Bataller, R., Sancho-Bru, P., Dominguez, M., Moreno, M., Forns, X., Bruguera, M., Arroyo, V., Brenner, D. A., Gines, P. Tags: LIVER AND BILIARY TRACT Source Type: journals
Homeostatic and therapeutic roles of VIP in smooth muscle function: myo-neuroimmune interactions
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We tested the hypothesis that spontaneous release of vasoactive intestinal peptide (VIP) from enteric neurons maintains homeostasis in smooth muscle function in mild inflammatory insults and that infusion of exogenous VIP has therapeutic effects on colonic smooth muscle dysfunction in inflammation. In vitro experiments were performed on human colonic circular smooth muscle tissues and in vivo on rats. The incubation of human colonic circular smooth muscle strips with TNF- suppressed their contractile response to ACh and the expression of the pore-forming 1C subunit of Cav1.2 channels. VIP reversed both effects by blocking ...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Shi, X.-Z., Sarna, S. K. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
Endocytic trafficking from the small intestinal brush border probed with FM dye
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The small intestinal brush border functions as the body's main portal for uptake of dietary nutrients and simultaneously acts as the largest permeability barrier against pathogens. To enable this, the digestive enzymes of the brush border are organized in lipid raft microdomains stabilized by cross-linking galectins and intelectin, but little is known about the dynamic properties of this highly specialized membrane. Here, we probed the endocytic membrane trafficking from the brush border of organ-cultured pig intestinal mucosal explants by use of a fixable, lipophilic FM dye. The fluorescent dye readily incorporated into t...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Hansen, G. H., Rasmussen, K., Niels-Christiansen, L.-L., Danielsen, E. M. Tags: MUCOSAL BIOLOGY Source Type: journals
Alternative splicing of the Menkes copper Atpase (Atp7a) transcript in the rat intestinal epithelium
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The intestinal Menkes copper Atpase (Atp7a) gene is strongly induced by iron deficiency in the rat intestine. We sought to develop an in vitro model to understand the mechanism of this induction by performing molecular studies in native rat intestine and in intestinal epithelial (IEC-6) cells. IEC-6 cells express Atp7a, and induction was noted with iron deprivation. 5' Rapid amplification of cDNA ends and PCR experiments revealed three splice variants in rat intestine and IEC-6 cells; all variants were strongly induced during iron deprivation (five- to sevenfold). The splice variants presumably encode proteins that would e...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Collins, J. F., Hua, P., Lu, Y., Ranganathan, P. N. Tags: MUCOSAL BIOLOGY Source Type: journals
Mg2+- and MgATP-inhibited and Ca2+/calmodulin-sensitive TRPM7-like current in hepatoma and hepatocytes
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Although understood to be ubiquitously expressed, the functional identification and significance of Mg2+-inhibited, nonspecific cation currents has been established in only a few cell types. Here we identified an outwardly rectifying nonspecific cation current in quiescent rat hepatocytes and the proliferating and polarized rat hepatoma, WIF-B. Under whole cell recording conditions in which cells were bathed and dialyzed with Na-gluconate solutions, the latter Ca2+ and Mg2+ free, current reversed close to 0 mV, was time independent, and was greater than 10 times higher at +120 mV compared with –120 mV. Outward curren...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Mishra, R., Rao, V., Ta, R., Shobeiri, N., Hill, C. E. Tags: LIVER AND BILIARY TRACT Source Type: journals
Hepatic uptake of {gamma}-butyrobetaine, a precursor of carnitine biosynthesis, in rats
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-Butyrobetaine (GBB) is a precursor in the biosynthesis of carnitine, which plays an important role in the β-oxidation of fatty acids, and is converted to carnitine by -butyrobetaine dioxygenase (BBD) predominantly in liver. We investigated the molecular mechanism of hepatic uptake of GBB in rat hepatocytes. Cellular localization of rat Octn2 (rOctn2:Slc22A5) was studied by Western blot analysis. Uptake of deuterated GBB (d3-GBB) was examined in HEK293 cells expressing rOctn2 (HEK293/rOctn2) and freshly isolated rat hepatocytes. d3-GBB was quantified by use of liquid chromatography-tandem mass spectrometry. Western bl...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Fujita, M., Nakanishi, T., Shibue, Y., Kobayashi, D., Moseley, R. H., Shirasaka, Y., Tamai, I. Tags: LIVER AND BILIARY TRACT Source Type: journals
Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach
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In this study, a biophysically based smooth muscle cell (SMC) model was modified on the basis of experimental data and employed in conjunction with experimental studies to define the effects of a large range of GES protocols on individual SMCs. For the validation studies, rat gastric SMCs were isolated and subjected to patch-clamp analysis during stimulation. Experimental results were in satisfactory agreement with simulation results. The results define the effects of a wide range of GES parameters (pulse width, amplitude, and pulse-train frequency) on isolated SMCs. The minimum pulse width required to invoke a supramechan...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Du, P., Li, S., O'Grady, G., Cheng, L. K., Pullan, A. J., Chen, J. D. Z. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats
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Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small i...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Hira, T., Mochida, T., Miyashita, K., Hara, H. Tags: HORMONES AND SIGNALING Source Type: journals
Extrinsic afferent nerve sensitivity and enteric neurotransmission in murine jejunum in vitro
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Enteric and extrinsic sensory neurons respond to similar stimuli. Thus they may be activated in series or in parallel. Because signal transmission via synapses or mediator release would depend on calcium, we investigated its role for extrinsic afferent sensitivity to chemical and mechanical stimulation. Extracellular multiunit afferent recordings were made in vitro from paravascular nerve bundles supplying the mouse jejunum. Intraluminal pressure and afferent nerve responses were recorded under control conditions and under four conditions designed to interfere with enteric neurotransmission. We found that phasic intestinal...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Mueller, M. H., Xue, B., Glatzle, J., Hahn, J., Grundy, D., Kreis, M. E. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
P2Y5 is a G{alpha}i, G{alpha}12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion
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This study elucidates a mechanism whereby LPA can act as a luminal and/or serosal cue to alter mucosal integrity. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Lee, M., Choi, S., Hallden, G., Yo, S. J., Schichnes, D., Aponte, G. W. Tags: HORMONES AND SIGNALING Source Type: journals
Intestinal cell kinase, a MAP kinase-related kinase, regulates proliferation and G1 cell cycle progression of intestinal epithelial cells
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In this study, we report that suppression of ICK expression in cultured intestinal epithelial cells by short hairpin RNA (shRNA) interference significantly impaired cellular proliferation and induced features of gene expression characteristic of colonic or enterocytic differentiation. Downregulation of ICK altered expression of cell cycle regulators (cyclin D1, c-Myc, and p21Cip1/WAF1) of G1-S transition, consistent with the G1 cell cycle delay induced by ICK shRNA. ICK deficiency also led to a significant decrease in the expression and/or activity of p70 ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor ...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Fu, Z., Kim, J., Vidrich, A., Sturgill, T. W., Cohn, S. M. Tags: MUCOSAL BIOLOGY Source Type: journals
Delayed restoration of Mg2+ content and transport in liver cells following ethanol withdrawal
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Liver cells from rats chronically fed a Lieber-De Carli diet for 3 wk presented a marked decreased in tissue Mg2+ content and an inability to extrude Mg2+ into the extracellular compartment upon stimulation with catecholamine, isoproterenol, or cell-permeant cAMP analogs. This defect in Mg2+ extrusion was observed in both intact cells and purified liver plasma membrane vesicles. Inhibition of adrenergic or cAMP-mediated Mg2+ extrusion was also observed in freshly isolated hepatocytes from control rats incubated acutely in vitro with varying doses of ethanol (EtOH) for 8 min. In this model, however, the defect in Mg2+ extru...
Source: AJP: Gastrointestinal and Liver Physiology - September 23, 2009 Category: Gastroenterology Authors: Torres, L. M., Cefaratti, C., Berti-Mattera, L., Romani, A. Tags: LIVER AND BILIARY TRACT Source Type: journals
Corrigendum
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(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 27, 2009 Category: Gastroenterology Tags: CORRIGENDUM Source Type: journals
Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-{kappa}B, and STAT3 signaling pathways
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Adiponectin is believed to exert hepatoprotective effects and induces CXCL8, a chemokine that functions as a survival factor, in vascular cells. In the current study, it is demonstrated that adiponectin also induces CXCL8 expression in primary human hepatocytes but not in hepatocellular carcinoma cell lines. Knock down of the adiponectin receptor (AdipoR) 1 or AdipoR2 by small-interfering RNA indicates that AdipoR1 is involved in adiponectin-stimulated CXCL8 release. Adiponectin activates nuclear factor (NF)-B in primary hepatocytes and pharmacological inhibition of NF-B, the p38 mitogen-activated protein kinase, and extra...
Source: AJP: Gastrointestinal and Liver Physiology - August 27, 2009 Category: Gastroenterology Authors: Wanninger, J., Neumeier, M., Weigert, J., Bauer, S., Weiss, T. S., Schaffler, A., Krempl, C., Bleyl, C., Aslanidis, C., Scholmerich, J., Buechler, C. Tags: HORMONES AND SIGNALING Source Type: journals
Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women
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In conclusion, in healthy women 1) gastric emptying of glucose is slower, and glycemia, plasma GLP-1 and insulin, hunger, and energy intake are less during the follicular compared with the luteal phase; 2) energy intake, glycemia, and plasma GLP-1 and insulin are related to gastric emptying; and 3) these parameters are reproducible when assessed twice during the follicular phase. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 27, 2009 Category: Gastroenterology Authors: Brennan, I. M., Feltrin, K. L., Nair, N. S., Hausken, T., Little, T. J., Gentilcore, D., Wishart, J. M., Jones, K. L., Horowitz, M., Feinle-Bisset, C. Tags: NEUROREGULATION AND MOTILITY Source Type: journals
