Regulation of Cl- Electrolyte Permeability in Epithelia by Active Traditional Chinese Medicine Monomers for Diarrhea

2020 ◽  
Vol 21 (9) ◽  
pp. 902-909
Author(s):  
Lei Chen ◽  
Yan Ding ◽  
Yapeng Hou ◽  
Yanhong Liu ◽  
Hongguang Nie
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Electrolyte Transport ◽  
Salt Flux ◽  
Intestinal Epithelial ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Epithelial Tissues ◽  
Water Secretion ◽  
Mucosal Side

The epithelial layer, lining the inner surface of the mammalian alveolar, kidney, brain and colon, is a typical electrolyte transporting tissue. Large quantities of salt and fluid are actively moved from the mucosal side toward the blood vessel. Transepithelial salt re-absorption in epithelial tissues plays an important role in maintaining fluid homeostasis. In absorptive epithelium, fluid and salt flux is controlled by the machinery mainly composed of epithelial sodium channel, cystic fibrosis transmembrane conductance regulator, Na+-K+-2Cl- cotransporter, Na+/H+ exchanger, and Na+/K+-ATPase. Dysregulation of salt permeability across epithelium contributes to the pathogenesis of organ edema. In numerous ion transporters, epithelial Cl- transportation plays an important role in water secretion across epithelial tissues and regulation of body fluid content. Many traditional Chinese medicines treat diarrhea by regulating the Cl- electrolyte transport. We systematically summarized the recent progress regarding the traditional Chinese medicine on Cl- electrolyte transport in the intestinal epithelial tissues. The pharmaceutical relevance of developing advanced strategies to mitigate edematous disorders is also implicated. In conclusion, the crosstalk between Cl- electrolyte transport and active traditional Chinese medicine monomers may lead to the development of new strategies for diarrhea by manipulating the function and expression of ion channels.

scholarly journals Linaclotide: A New Option for the Treatment of Irritable Bowel syndrome with Constipation and Chronic Idiopathic Constipation in Adults

2013 ◽  
Vol 6 ◽  
pp. CGast.S10550 ◽  
Author(s):  
Colleen H. Parker ◽  
Yuhong Yuan ◽  
Louis Wing Cheong Liu
Keyword(s):  
Irritable Bowel Syndrome ◽  
Functional Gastrointestinal Disorders ◽  
Cochrane Central Register ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Idiopathic Constipation ◽  
Chronic Idiopathic Constipation ◽  
Central Register ◽  
Water Secretion ◽  
Irritable Bowel

Chronic idiopathic constipation (CC) and irritable bowel syndrome with predominant constipation (IBS-C) are the 2 most common conditions among functional gastrointestinal disorders. Despite current multiple therapeutic options, treatment remains challenging and dissatisfactory to many patients. Linaclotide is a novel therapeutic agent, which is a guanylate cyclase receptor agonist that stimulates water secretion from the intestinal epithelium by promoting chloride and bicarbonate efflux into the lumen through activation of the cystic fibrosis transmembrane conductance regulator. Clinical trials have demonstrated that linaclotide is effective, safe and well tolerated in patients with CC and IBS-C. This review article highlights the mechanism of action of linaclotide, reviews published literature based on a search of databases, including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), up to February 2013, and compares its utility with other currently available agents.

scholarly journals Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice

2001 ◽  
Vol 281 (3) ◽  
pp. G681-G687 ◽  
Author(s):  
Ann Marie Gallagher ◽  
Roberta A. Gottlieb
Keyword(s):  
Cell Proliferation ◽  
Small Intestine ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Intestinal Epithelial ◽  
Transmembrane Conductance Regulator ◽  
Epithelial Cell Proliferation ◽  
Transmembrane Conductance ◽  
Epithelial Cell Migration

Expression of a mutated cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to enhance proliferation within CF airways, and cells expressing a mutated CFTR have been shown to be less susceptible to apoptosis. Because the CFTR is expressed in the epithelial cells lining the gastrointestinal tract and all CF mouse models are characterized by gastrointestinal obstruction, we hypothesized that CFTR null mice would have increased epithelial cell proliferation and reduced apoptosis within the small intestine. The rate of intestinal epithelial cell migration from crypt to villus was increased in CFTR null mice relative to mice expressing the wild-type CFTR. This difference in migration could be explained by an increase in epithelial cell proliferation but not by a difference in apoptosis within the crypts of Lieberkühn. In addition, using two independent sets of CF cell lines, we found that epithelial cell susceptibility to apoptosis was unrelated to the presence of a functional CFTR. Thus increased proliferation but not alterations in apoptosis within epithelial cells might contribute to the pathophysiology of CF.

NSP4 elicits age-dependent diarrhea and Ca2+mediated I−influx into intestinal crypts of CF mice

1999 ◽  
Vol 277 (2) ◽  
pp. G431-G444 ◽  
Author(s):  
Andrew P. Morris ◽  
Jason K. Scott ◽  
Judith M. Ball ◽  
Carl Q.-Y. Zeng ◽  
Wanda K. O’Neal ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Intestinal Epithelial ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Gene Encoding ◽  
Gastrointestinal Complications ◽  
Age Dependent ◽  
Intracellular Ca ◽  
Cf Transmembrane Conductance Regulator ◽  
Mouse Pup

Homologous disruption of the murine gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) leads to the loss of cAMP-mediated ion transport. Mice carrying this gene defect exhibit meconium ileus at birth and gastrointestinal plugging during the neonatal period, both contributing to high rates of mortality. We investigated whether infectious mammalian rotavirus, the recently characterized rotaviral enterotoxin protein NSP4, or its active NSP4114–135peptide, can overcome these gastrointestinal complications in CF (CFTRm3Baynull mutation) mice. All three agents elicited diarrhea when administered to wild-type (CFTR+/+), heterozygous (CFTR+/−), or homozygous (CFTR−/−) 7- to 14-day-old mouse pups but were ineffective when given to older mice. The diarrheal response was accompanied by non-age-dependent intracellular Ca2+mobilization within both small and large intestinal crypt epithelia. Significantly, NSP4 elicited cellular I−influx into intestinal epithelial cells from all three genotypes, whereas both carbachol and the cAMP-mobilizing agonist forskolin failed to evoke influx in the CFTR−/−background. This unique plasma membrane halide permeability pathway was age dependent, being observed only in mouse pup crypts, and was abolished by either the removal of bath Ca2+or the transport inhibitor DIDS. These findings indicate that NSP4 or its active peptide may induce diarrhea in neonatal mice through the activation of an age- and Ca2+-dependent plasma membrane anion permeability distinct from CFTR. Furthermore, these results highlight the potential for developing synthetic analogs of NSP4114–135to counteract chronic constipation/obstructive bowel syndrome in CF patients.

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