The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Helen J Cooke - One of the best experts on this subject based on the ideXlab platform.
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neurotransmitters in neuronal reflexes regulating Intestinal Secretion
Annals of the New York Academy of Sciences, 2006Co-Authors: Helen J CookeAbstract:: The Intestinal crypt cell secretes chloride into the lumen, resulting in accumulation of fluid that normally thins out mucus or, at higher secretory rates, flushes out the contents. The regulation of chloride Secretion occurs by neural reflex pathways within the enteric nervous system. Mechanical stimulation releases 5-hydroxytryptamine (5-HT) from enterochromaffin cells with subsequent activation of intrinsic primary afferents that carry electrical signals to submucosal ganglia. After processing, interneurons activate cholinergic and vasoactive Intestinal peptide (VIP) secretomotor neurons. Acetylcholine and VIP bind to epithelial receptors and stimulate sodium chloride and fluid Secretion. Reflex-evoked secretory rates can be modulated by a variety of mediators at the level of the enterochromaffin cells, neurons within the reflex pathway, or epithelial cells. Understanding the complex regulatory mechanisms for chloride Secretion is likely to provide mechanistic insights into constipation and diarrhea.
Michael Camilleri - One of the best experts on this subject based on the ideXlab platform.
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Guanylate cyclase C signaling: an Intestinal secretory pathway where bugs, genes and new drugs intersect
Genome Medicine, 2012Co-Authors: Michael CamilleriAbstract:Acute infectious and chronic diarrheal diseases are important public health problems. A recent study by Fiskerstrand and colleagues identified a family with a rare early onset familial diarrhea. By linkage analysis and exon sequencing, the authors identified a heterozygous missense mutation in GUCY2C , encoding the guanylate cyclase C receptor, which is involved in Intestinal Secretion. This newly identified gene in the etiology of a familial diarrhea provides a candidate target for the development not only of new treatments for diarrhea, but also of a new drug class to treat constipation.
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effect of a selective chloride channel activator lubiprostone on gastroIntestinal transit gastric sensory and motor functions in healthy volunteers
American Journal of Physiology-gastrointestinal and Liver Physiology, 2006Co-Authors: Michael Camilleri, Kari Baxter, Sanna Mckinzie, Duane Burton, Ryuji Ueno, Adil E. Bharucha, George M Thomforde, Alan R. ZinsmeisterAbstract:Chloride channels modulate gastroIntestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces Intestinal Secretion and has been shown to...
Jean Paul Galmiche - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of prostaglandin-induced Intestinal Secretion by igmesine in healthy volunteers ☆ ☆☆
Gastroenterology, 1998Co-Authors: Claude Rozé, Stanislas Bruley Des Varannes, Jean Genève, Jean Paul GalmicheAbstract:Abstract Background & Aims: Igmesine, a σ ligand, has been shown to inhibit Intestinal Secretion and diarrhea in animal models. The purpose of this study was to measure the inhibitory effect of igmesine on basal and prostaglandin E 2 (PGE 2 )-induced jejunal Secretion in normal volunteers. Methods: Jejunal absorption of water and electrolytes was measured with a three-lumen open-segment perfusion method in 16 volunteers. A double-blind crossover study was performed involving intraluminal infusion of PGE 2 after oral administration of placebo or igmesine at two doses. Results: PGE 2 induced net Secretion of water and electrolytes ( P 2 on water and electrolytes was not changed by 25 mg of igmesine but was suppressed by 200 mg of igmesine. This effect lasted at least 3 hours after a single oral dose. Igmesine at a dose of 200 mg also produced a significant decrease in basal rates of water and electrolyte absorption. Conclusions: Igmesine, a σ ligand, inhibits PGE 2 -induced Intestinal Secretion in normal humans. Evaluating the drug in chronic diarrheas may be of interest. GASTROENTEROLOGY 1998;115:591-596
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Peptide YY Inhibition of Prostaglandin-Induced Intestinal Secretion Is Haloperidol-Sensitive in Humans
Gastroenterology, 1997Co-Authors: Claude Rozé, Jean Genève, C Molis, Fc Xiaomei, A. Ropert, Jean Paul GalmicheAbstract:BACKGROUND & AIMS: It is uncertain whether peptide YY (PYY) inhibits human Intestinal Secretion directly through enterocyte receptors or via indirect neural mechanisms. Thus, the effect of PYY on prostaglandin E2 (PGE2)-induced jejunal Secretion in normal volunteers was measured, and it was determined whether a dopamine and sigma antagonist affected PYY effect. METHODS: Jejunal absorption of water and electrolytes was measured by a perfusion method in 6 volunteers. A double-blind crossover study was performed, involving intraluminal infusion of PGE2, intravenous infusion of human PYY, and intramuscular injection of haloperidol or placebo. RESULTS: PGE2 induced net Secretion of water and electrolytes (P < 0.01 vs. basal). The effect of PGE2 was reduced by about half with 30 pmol x kg(-1) x h(-1) of PYY (plasma PYY, 96 +/- 12 pg/mL) and suppressed by 90 pmol x kg(-1) x h(-1) of PYY (P < 0.01; plasma PYY, 268 +/- 22 pg/mL). Plasma PYY was correlated negatively (P < 0.01) with net fluxes of water, Cl-, Na+, and K+. Haloperidol suppressed the effect of PYY on PGE2-induced Secretion (P < 0.05). CONCLUSIONS: PYY administered in doses producing slightly supraphysiological plasma levels inhibits PGE2-induced Secretion in normal humans. Sigma or dopamine receptors (probably neuronal ones) are involved in this effect. (Gastroenterology 1997 May;112(5):1520-8)
Alan R. Zinsmeister - One of the best experts on this subject based on the ideXlab platform.
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effect of a selective chloride channel activator lubiprostone on gastroIntestinal transit gastric sensory and motor functions in healthy volunteers
American Journal of Physiology-gastrointestinal and Liver Physiology, 2006Co-Authors: Michael Camilleri, Kari Baxter, Sanna Mckinzie, Duane Burton, Ryuji Ueno, Adil E. Bharucha, George M Thomforde, Alan R. ZinsmeisterAbstract:Chloride channels modulate gastroIntestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces Intestinal Secretion and has been shown to...
Scott A Waldman - One of the best experts on this subject based on the ideXlab platform.
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Intestinal enteroids model guanylate cyclase c dependent Secretion induced by heat stable enterotoxins
Infection and Immunity, 2016Co-Authors: Amanda M Pattison, Erik S Blomain, Dante J Merlino, Fang Wang, Mary Ann S Crissey, Crystal L Kraft, Jeffrey A Rappaport, Adam E Snook, John P Lynch, Scott A WaldmanAbstract:ABSTRACT Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the Intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced Intestinal Secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human Intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced Intestinal Secretion. Enteroid Secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid Secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid Secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease.
