Molecular and functional studies of electrogenic Na+ transport in the distal colon and rectum of young and elderly subjects

Greig, Emma; Mathialahan, T.; Boot-Handford, Raymond P.; Sandle, Geoffrey I.

doi:10.1136/gut.52.11.1607

Cited by 13 publications

(13 citation statements)

References 51 publications

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“…γ‐subunit antibody, raised in rabbit against apical Na + channel protein from bovine renal papilla 15, 18, was applied at 1 : 60 dilution. ENaC antibodies were detected using the avidin–biotin complex technique 14. In keeping with electrophysiological studies 19, antibodies to ENaC subunits were localized to the apical membrane of surface cells but not crypt cells in non‐inflamed colonic mucosa (see the Results section).…”

Section: Methodsmentioning

confidence: 75%

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Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis

Boot-Handford

Mani

et al. 2004

The Journal of Pathology

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Impaired absorption of sodium (Na+) and water is a major factor in the pathogenesis of diarrhoea in ulcerative colitis (UC). Electrogenic Na+ absorption, present mainly in human distal colon and rectum, is defective in UC, but the molecular basis for this is unclear. The effect of UC on the expression of apical Na+ channels (ENaC) and basolateral Na+, K+-ATPase, the critical determinants of electrogenic Na+ transport, was therefore investigated in this study. Sigmoid colonic and/or proximal rectal mucosal biopsies were obtained from patients with mild to moderate UC, and patients with functional abdominal pain (controls). ENaC subunit expression was studied by immunohistochemistry, western blot analysis, and in situ hybridization, and Na+, K+-ATPase isoform expression was studied by immunohistochemistry, western blotting, and northern blot analysis. UC was associated with substantial decreases in the expression of the ENaC beta- and gamma-subunit proteins and mRNAs, whereas the decrease in ENaC alpha-subunit protein detected by immunolocalization was less marked. The levels of expression of Na+, K+-ATPase alpha1- and beta1-isoform proteins were also lower in UC patients than in controls, although there were no differences in Na+, K+-ATPase alpha1- and beta1-isoform mRNA levels between the two groups. Taken together, these results show that UC results mainly in decreased expression of the apical ENaC beta- and gamma-subunits, as well as the basolateral Na+, K+-ATPase alpha1- and beta1-isoforms. In conclusion, these changes provide a basis for the low/negligible levels of electrogenic Na+ absorption seen in the distal colon and rectum of UC patients, which contribute to the pathogenesis of diarrhoea in this disease.

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Section: Methodsmentioning

confidence: 75%

“…Colonic biopsies were processed and 6 µm sections were cut 14. Sections were incubated in phosphate‐buffered saline (pH 7.2) at 37 °C overnight and at 60 °C for 1 h immediately before use.…”

Section: Methodsmentioning

confidence: 99%

Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis

Boot-Handford

Mani

et al. 2004

The Journal of Pathology

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“…These studies provided evidence for the localization of ENaC in kidney, lung, salivary glands, skin, placenta and the colon. Expression of ENaC subunits has been also examined by in situ hybridization of tissue sections using cDNA probes (Greig et al, 2003). But, this approach does not provide an image of the intracellular localization of the subunits themselves.…”

Section: Tissue Distribution Of Enacmentioning

confidence: 99%

Epithelial sodium channel (ENaC) family: Phylogeny, structure–function, tissue distribution, and associated inherited diseases

Hanukoglu

2016

Gene

349

345

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The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na+ ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na+ in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension.

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“…Very early studies suggested that atrophy of the colonic mucosa occurs with advancing age [16] , associated with alterations in water and electrolyte transport. Renal responses to sodium restriction are impaired in the elderly [17] ; however in a recent study, mineralocorticoid-sensitive electrogenic sodium absorption was not lower in biopsies from the colon of human volunteers over the age of seventy [18] . The absorption of metal ions as a function of age has not received much attention; however, a recent report of careful studies in the rat suggests that zinc absorption may be considerably decreased, magnesium absorption decreased only moderately, and copper absorption is unaffected [19] .…”

Section: Intestinal Micronutrient Absorptionmentioning

confidence: 99%

Intestinal Malabsorption in the Elderly

Holt¹

2007

Dig Dis

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Background: Intestinal malabsorption in the elderly is infrequent, and clinical features are muted so that the diagnosis is often missed. Physiologic changes with aging are restricted to altered absorption of calcium and perhaps zinc and magnesium; however, achlorhydria can lead to impaired absorption of vitamin B₁₂, folic acid, and calcium. Methods and Results: Small bowel bacterial overgrowth occurs more commonly in elderly than in younger patients, accompanying gastric hypochlorhydria, altered intestinal motor activity, or diseases such as Parkinson’s disease. Changes in pancreatic anatomy and secretion occur but are insufficient to produce macronutrient malabsorption. In addition to pancreatic cancer and pancreatic stones, older patients may present with severe pancreatic insufficiency of unknown etiology. Celiac disease is recognized as very common at all ages and may not become evident until late in life. Manifestations of celiac disease in the elderly are occult and the diagnosis often is not considered until serologic tests are performed and confirmed by upper small intestinal biopsy. Associated intestinal lymphoma, esophageal carcinoma, intestinal pseudo-obstruction, and splenic atrophy may be more common in the elderly. Treatment of older patients with celiac disease with a gluten-free diet may be difficult, and intensive vitamin and micronutrient replacement is mandatory. A pragmatic approach to the evaluation of malabsorption in elderly patients is discussed.

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Molecular and functional studies of electrogenic Na+ transport in the distal colon and rectum of young and elderly subjects

Cited by 13 publications

References 51 publications

Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis

Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis

Epithelial sodium channel (ENaC) family: Phylogeny, structure–function, tissue distribution, and associated inherited diseases

Intestinal Malabsorption in the Elderly

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Molecular and functional studies of electrogenic Na+ transport in the distal colon and rectum of young and elderly subjects

Cited by 13 publications

References 51 publications

Decreased expression of apical Na+ channels and basolateral Na+, K+‐ATPase in ulcerative colitis

Decreased expression of apical Na+ channels and basolateral Na+, K+‐ATPase in ulcerative colitis

Epithelial sodium channel (ENaC) family: Phylogeny, structure–function, tissue distribution, and associated inherited diseases

Intestinal Malabsorption in the Elderly

Contact Info

Product

Resources

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Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis

Decreased expression of apical Na⁺ channels and basolateral Na⁺, K⁺‐ATPase in ulcerative colitis