Molecular Mechanisms of Disturbed Electrolyte Transport in Intestinal Inflammation

Abstract

Diarrhea is the hallmark of both ulcerative colitis (UC) and Crohn's disease. Loss of resorptive area, destruction of epithelial cells, leaky tight junctions, and release of inflammatory mediators and products from immune cells that stimulate fluid secretion all have been implicated in the pathogenesis of inflammatory diarrhea. Very early studies in patients, however, have pinpointed the overwhelming transport abnormality in inflamed intestinal mucosa: a virtually complete loss of sodium resorptive capacity. Recently, tools have become available to study the molecular basis of disturbances in the major electrolyte transport systems during intestinal inflammation. This review gives a brief overview of the historical development of research related to electrolyte transport in inflammatory bowel disorders, focusing on the studies performed in humans, and highlights recent understanding of the molecular mechanisms that may help explain the origin of diarrhea in intestinal inflammation.

Reciprocal regulation of the primary sodium absorptive pathways in rat intestinal epithelial cells

“…In view of the significance of these two transport proteins in mammalian intestinal physiology, many studies have been conducted involving their regulation in health and in disease (21,32). However, no study has been undertaken to determine whether the expression and activity of these two transporters found on the BBM of the villus cells function together to regulate sodium absorption.…”

Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate

“…In this regard, previous studies from our laboratory and others have shown dysregulation of DRA function and expression in the pathogenesis of diarrhea associated with inflammation (33,38,39) or enteric infections Ϫ exchanger, did not change, indicating that the effects of S1P are specific to DRA. Previous studies have demonstrated that DRA and PAT-1 mRNA are expressed along the entire length of the intestine with regional and surface-crypt axis differences in their protein expression patterns (25).…”

News from the End of the Gut-How the Highly Segmental Pattern of Colonic HCO3- Transport Relates to Absorptive Function and Mucosal Integrity

“…Intestinal Inflammation Dysregulated ion transport plays a key role for diarrhea development in inflammatory bowel disease (IBD). The molecular mechanisms of inflammatory diarrhea have been recently reviewed, [115][116][117][118] with emphasis on the mechanisms for decreased Na ϩ absorption and the loss of tight junctional integrity. After early studies had demonstrated a shift of the rectal potential difference (PD) to positive values during acute flare-ups of ulcerative colitis, 119) which may point to changes in electrogenic anion secretion, intestinal Cl Ϫ secretion was investigated in Ussing chambers.…”

“…After early studies had demonstrated a shift of the rectal potential difference (PD) to positive values during acute flare-ups of ulcerative colitis, 119) which may point to changes in electrogenic anion secretion, intestinal Cl Ϫ secretion was investigated in Ussing chambers. When inflammatory mediators were applied to healthy intestinal mucosa, a secretory response was frequently observed (reviewed in 115) ). However, inflamed colonic mucosa from UC patients was found to display defective Cl Ϫ secretory response to agonists.…”