scholarly journals Alterations to enteric neural signaling underlie secretory abnormalities of the ileum in experimental colitis in the guinea pig

2009 ◽  
Vol 296 (4) ◽  
pp. G717-G726 ◽  
Author(s):  
Ian M. Hons ◽  
Joshua E. Burda ◽  
John R. Grider ◽  
Gary M. Mawe ◽  
Keith A. Sharkey
Keyword(s):  
Synaptic Transmission ◽  
Ion Transport ◽  
Action Potentials ◽  
Experimental Colitis ◽  
Trinitrobenzene Sulfonic Acid ◽  
Contributing Factors ◽  
Ileal Mucosa ◽  
Ussing Chambers ◽  
Electrogenic Ion Transport ◽  
Secretomotor Neurons

Inflammatory bowel diseases (IBD) can involve widespread gastrointestinal dysfunction, even in cases in which inflammation is localized to a single site. The underlying pathophysiology of dysfunction in noninflamed regions is unclear. We examined whether colitis is associated with altered electrogenic ion transport in the ileal mucosa and/or changes in the properties of ileal submucosal neurons. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS), and the uninflamed ileum from animals was examined 3, 7, and 28 days later. Electrogenic ion transport was assessed in Ussing chambers. Intracellular microelectrode recordings were used to examine the neurophysiology of the submucosal plexus of the ileum in animals with colitis. Noncholinergic secretion was reduced by 33% in the ileum from animals 7 days after the induction of colitis. The epithelial response to vasoactive intestinal peptide (VIP) was unaltered in animals with colitis, but the response to carbachol was enhanced. Slow excitatory synaptic transmission was dramatically reduced in VIP-expressing, noncholinergic secretomotor neurons. This change was detected as early as 3 days following TNBS treatment. No changes to fast synaptic transmission or the number of VIP neurons were observed. In addition, cholinergic secretomotor neurons fired more action potentials during a given stimulus, and intrinsic primary afferent neurons had broader action potentials in animals with colitis. These findings implicate changes to enteric neural circuits as contributing factors in inflammation-induced secretory dysfunction at sites proximal to a localized inflammatory insult.

scholarly journals Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?

2009 ◽  
Vol 297 (5) ◽  
pp. G869-G877 ◽  
Author(s):  
Niall P. Hyland ◽  
Adam P. Chambers ◽  
Catherine M. Keenan ◽  
Quentin J. Pittman ◽  
Keith A. Sharkey
Keyword(s):  
Intestinal Inflammation ◽  
Control Diet ◽  
Plasminogen Activator Inhibitor ◽  
Experimental Colitis ◽  
Trinitrobenzene Sulfonic Acid ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fourfold Increase ◽  
Ussing Chambers ◽  
Epithelial Physiology ◽  
Pai 1

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 physiology was assessed using Ussing chambers. DIO rats had a modestly increased circulating PAI-1 before TNBS treatment; however, during colitis, DR animals had more than a fourfold increase in circulating PAI-1 compared with DIO rats. Circulating leptin was higher in DIO rats compared with DR animals, in the inflamed and noninflamed states. These changes in TNBS-induced adipokine profile were accompanied by decreased macroscopic tissue damage score in DIO animals compared with DR tissues. Furthermore, TNBS-treated DR animals lost significantly more weight than DIO rats during active inflammation. Colonic epithelial physiology was comparable between groups, as was MPO activity. The factors contributing to the decreased colonic damage are almost certainly multifold, driven by both genetic and environmental factors, of which adipokines are likely to play a part given the increasing body of evidence for their role in modulating intestinal inflammation.

HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway

2021 ◽  
Author(s):  
Yong Fu ◽  
Gailing Ma ◽  
Yuqian Zhang ◽  
Wenli Wang ◽  
Tongguo Shi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Camp Response Element Binding ◽  
Cellular Level ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Colitis ◽  
Anti Inflammatory

Abstract Background Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that plays a pivotal role in maintaining mucosal immune homeostasis. As a novel synthetic inhibitor of salt-inducible kinases (SIKs), HG-9-91-01 can effectively enhance IL-10 secretion at the cellular level, but its in vivo immunoregulatory effects remain unclear. In this study, we investigated the effects and underlying mechanism of HG-9-91-01 in murine colitis models. Methods The anti-inflammatory effects of HG-9-91-01 were evaluated on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium–induced colitis mice, and IL-10 knockout chronic colitis mice. The in vivo effector cell of HG-9-91-01 was identified by fluorescence-activated cell sorting and quantitative real-time polymerase chain reaction. The underlying mechanism of HG-9-91-01 was investigated via overexpressing SIKs in ANA-1 macrophages and TNBS colitis mice. Results Treatment with HG-9-91-01 showed favorable anticolitis effects in both TNBS- and DSS-treated mice through significantly promoting IL-10 expression in colonic macrophages but failed to protect against IL-10 KO murine colitis. Further study indicated that HG-9-91-01 markedly enhanced the nuclear level of cAMP response element-binding protein (CREB)-regulated transcription coactivator 3 (CRTC3), whereas treatment with lentiviruses encoding SIK protein markedly decreased the nuclear CRTC3 level in HG-9-91-01–treated ANA-1 macrophages. In addition, intracolonic administration with lentiviruses encoding SIK protein significantly decreased the nuclear CRTC3 level in the lamina propria mononuclear cells and ended the anti-inflammatory activities of HG-9-91-01. Conclusions We found that HG-9-91-01 promoted the IL-10 expression of colonic macrophages and exhibited its anticolitis activity through the SIK/CRTC3 axis, and thus it may represent a promising strategy for inflammatory bowel disease therapy.

Elementary auxin response chains at the plasma membrane involve external abp1 and multiple electrogenic ion transport proteins

1996 ◽  
Vol 18 (1-2) ◽  
pp. 23-28 ◽  
Author(s):  
H�l�ne Barbier-Brygoo ◽  
Sabine Zimmermann ◽  
S�bastien Thomine ◽  
Ian R. White ◽  
Paul Millner ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ion Transport ◽  
Transport Proteins ◽  
Auxin Response ◽  
Electrogenic Ion Transport ◽  
Response Chains

Development of Excitatory Circuitry in the Hippocampus

1998 ◽  
Vol 79 (4) ◽  
pp. 2013-2024 ◽  
Author(s):  
Albert Y. Hsia ◽  
Robert C. Malenka ◽  
Roger A. Nicoll
Keyword(s):  
Synaptic Transmission ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Excitatory Synaptic Transmission ◽  
Developmental Strategy ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Quantal Size ◽  
Physiological Approach ◽  
Local Circuitry

Hsia, Albert Y., Robert C. Malenka, and Roger A. Nicoll. Development of excitatory circuitry in the hippocampus. J. Neurophysiol. 79: 2013–2024, 1998. Assessing the development of local circuitry in the hippocampus has relied primarily on anatomic studies. Here we take a physiological approach, to directly evaluate the means by which the mature state of connectivity between CA3 and CA1 hippocampal pyramidal cells is established. Using a technique of comparing miniature excitatory postsynaptic currents (mEPSCs) to EPSCs in response to spontaneously occurring action potentials in CA3 cells, we found that from neonatal to adult ages, functional synapses are created and serve to increase the degree of connectivity between CA3-CA1 cell pairs. Neither the probability of release nor mean quantal size was found to change significantly with age. However, the variability of quantal events decreases substantially as synapses mature. Thus in the hippocampus the developmental strategy for enhancing excitatory synaptic transmission does not appear to involve an increase in the efficacy at individual synapses, but rather an increase in the connectivity between cell pairs.

scholarly journals Enterohemorrhagic E. coli (EHEC)—Secreted Serine Protease EspP Stimulates Electrogenic Ion Transport in Human Colonoid Monolayers

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 351 ◽  
Author(s):  
C. Tse ◽  
Julie In ◽  
Jianyi Yin ◽  
Mark Donowitz ◽  
Michele Doucet ◽  
...  
Keyword(s):  
Ion Transport ◽  
Serine Protease ◽  
Shiga Toxin ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Adult Stem Cell ◽  
Short Circuit Current ◽  
Watery Diarrhea ◽  
E Coli ◽  
Electrogenic Ion Transport

One of the characteristic manifestations of Shiga-toxin-producing Escherichia coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components of the type-3 secretion system have been found to independently elicit fluid secretion. We used the adult stem-cell-derived human colonoid monolayers (HCM) to test whether EHEC-secreted extracellular serine protease P (EspP), a member of the serine protease family broadly expressed by diarrheagenic E. coli can act as an enterotoxin. We applied the Ussing chamber/voltage clamp technique to determine whether EspP stimulates electrogenic ion transport indicated by a change in short-circuit current (Isc). EspP stimulates Isc in HCM. The EspP-stimulated Isc does not require protease activity, is not cystic fibrosis transmembrane conductance regulator (CFTR)-mediated, but is partially Ca2+-dependent. EspP neutralization with a specific antibody reduces its potency in stimulating Isc. Serine Protease A, secreted by Enteroaggregative E. coli, also stimulates Isc in HCM, but this current is CFTR-dependent. In conclusion, EspP stimulates colonic CFTR-independent active ion transport and may be involved in the pathophysiology of EHEC diarrhea. Serine protease toxins from E. coli pathogens appear to serve as enterotoxins, potentially significantly contributing to watery diarrhea.

scholarly journals 191 Early weaning in pigs induces long-term alterations in intestinal nutrient transporter function and expression partially via beta adrenergic enteric neural receptors

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 112-113
Author(s):  
Yihang Li ◽  
Karina Matos ◽  
Mrigendra Rajput ◽  
Adam James Moeser
Keyword(s):  
Adrenergic Receptor ◽  
Glucose Transporter ◽  
Short Circuit ◽  
Na Channel ◽  
Early Weaning ◽  
Ileal Mucosa ◽  
Ussing Chambers ◽  
New Findings ◽  
Nutrient Transporter

Abstract Early weaning (EW) has negative impacts on performance and health that persist from wean-to-finish. The mechanisms linking EW and lifetime performance reductions are poorly understood. The objective of this study was to investigate whether EW influences the long-term development of intestinal epithelial nutrient transporter function and expression and the potential mechanisms. Yorkshire gilts were split-weaned from their sows at 15 d (EW) or 28 d of age (Late Weaning; LW) and transferred to an on-site nursery room. All pigs received the same diets in a standard phase feeding program and were euthanized at 75 d of age. Mid-jejunum and distal ileum were mounted on Ussing chambers to evaluate Na+-dependent glucose and amino acid (AA) transporter function, measured as nutrient-induced changes in short circuit current (Isc). EW gilts exhibited reduced capacity for electrogenic transport of glucose (by ~30%; P < 0.05) and glutamate, glutamine, and alanine by (~ 30–35%; P < 0.05), compared with LW pigs. In contrast, jejunal and ileal lysine transporter function was upregulated (by 110% and 25%, respectively; P < 0.05) in EW pigs. Epithelial expression for glucose transporter (SGLT1) was reduced (P < 0.05) while glucose/fructose transporter (GLUT2), fructose transporter (GLUT5) and lysine transporters (B0AT1, CAT1, and ATB0, +) were enhanced in the EW jejunum. No differences observed in villus morphology between EW and LW pigs. Pretreatment of ileal mucosa on Ussing chambers with the Na+ channel blocker (Tetrodotoxin) or the β-adrenergic receptor blocker (Propranolol) augmented glucose, lysine and alanine transporter function in EW but not LW pigs. Together, these data show that EW in gilts induces lasting and divergent alterations in intestinal nutrient transporter function and expression which is mediated in part by the enteric nervous system and β-adrenergic receptor pathways. These new findings may explain why EW pigs exhibit lasting deleterious impacts on performance. Further mechanism-based investigations could reveal new targets for optimizing performance in EW pigs throughout the production lifespan.

scholarly journals Effect of Cholera Enterotoxin on Ion Transport across Isolated Ileal Mucosa

1972 ◽  
Vol 51 (4) ◽  
pp. 796-804 ◽  
Author(s):  
Michael Field ◽  
David Fromm ◽  
Qais Al-Awqati ◽  
William B. Greenough
Keyword(s):  
Ion Transport ◽  
Ileal Mucosa ◽  
Cholera Enterotoxin

Evidence for an electrogenic ion transport pump in cells of higher plants

1970 ◽  
Vol 3 (1) ◽  
pp. 210-222 ◽  
Author(s):  
N. Higinbotham ◽  
J. S. Graves ◽  
R. F. Davis
Keyword(s):  
Ion Transport ◽  
Higher Plants ◽  
Electrogenic Ion Transport ◽  
In Cells

The application of Ussing chambers for determining the impact of microbes and probiotics on intestinal ion transport

2013 ◽  
Vol 91 (9) ◽  
pp. 663-670 ◽  
Author(s):  
Kevin W. Lomasney ◽  
Niall P. Hyland
Keyword(s):  
Ion Transport ◽  
Animal Studies ◽  
Ussing Chamber ◽  
Positive Influence ◽  
Mechanisms Of Action ◽  
Ussing Chambers ◽  
Host Microbe Interactions ◽  
The Impact ◽  
Intestinal Ion Transport

Host–microbe interactions have gained considerable attention in recent years with regards to their role in various organic disorders and diseases. In particular, research efforts have focused on the intestinal microbiota, where the largest and most diverse populations not only co-exist with the host, but also directly influence the state and function of the gastrointestinal (GI) tract. Moreover, both human and animal studies alike are now beginning to show a positive influence of probiotic bacteria on GI disorders associated with diarrhoea or constipation. Diarrheagenic GI diseases, such as those caused by Vibreo cholera or enterpathogenic Eschericia coli, have well-characterised interactions with the host that explain much of the observed symptoms, in particular severe diarrhoea. However, the mechanisms of action of nonpathogenic bacteria or probiotics on host physiology are less clearly understood. In the context of defining the mechanisms of action of probiotics in vitro, the Ussing chamber has proven to be a particularly useful tool. Here, we will present data from several studies that have defined molecular targets for microbes and putative probiotics in the regulation of intestinal secretory and absorptive function, and we will discuss these in the context of their application in pathogen- or inflammation-induced alterations in intestinal ion transport.

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