Cellular basis for defective electrolyte transport in inflamed human colon.
Electrolyte transport pathways in distal colonic mucosa from patients with noninflammatory and inflammatory (ulcerative colitis, Crohn's colitis) disease of the large bowel were studied in vitro with electrophysiological techniques. Noninflamed tissues exhibited substantial amiloride-sensitive electrogenic sodium transport. In contrast, inflamed but structurally intact tissues exhibited only a modest degree of electrogenic sodium transport, significant increases in total tissue conductance and apical membrane conductance, and a 100% increase in the arachidonic acid content of the cell membrane fraction of mucosal homogenates. Replacement of chloride with gluconate decreased total tissue conductance to a greater extent in inflamed than in noninflamed tissues, and total tissue conductance was higher in inflamed than in noninflamed tissues in the presence of transepithelial potassium and sodium gradients, suggesting enhanced mucosal "leakiness" to anions and cations in acute colitis. Apical addition of nystatin virtually abolished amiloride-sensitive apical sodium uptake in both groups, indicating that the ionophore formed channels in the apical membrane of noninflamed and diseased mucosa. Additional studies showed that mucosal inflammation decreased maximal activity of the basolateral sodium pump by 76%. Thus, defects in the biophysical properties of colonic epithelial cell membranes are likely to be important factors in the pathogenesis of diarrhea in ulcerative and Crohn's colitis.
Sandle
G I
GI
Epithelial Membrane Research Centre, University of Manchester, Salford, England.
Higgs
N
N
Crowe
P
P
Marsh
M N
MN
Venkatesan
S
S
Peters
T J
TJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D004573:Electrolytes / Q000378:metabolism*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000032:analysis; D008875:Middle Aged; D009761:Nystatin / Q000494:pharmacology
D004573:Electrolytes; D008563:Membrane Lipids; D009761:Nystatin