2014
DOI: 10.1007/s00424-014-1560-9
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Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

Abstract: Abstract:Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhea. In this study our aim was to characterise the cellular pathomechanism of bile-induced diarrhea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileumresected pati… Show more

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Cited by 14 publications
(17 citation statements)
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“…); and bile acid‐mediated mobilisation of Ca 2+ via IP 3 Rs was also observed in human colonic crypts (Pallagi‐Kunstar et al . ). In PSCs, however, it would appear that the initial release of Ca 2+ from the intracellular stores very quickly leads to depletion of the ER, which triggers opening of store‐operated Ca 2+ entry (SOCE) channels in the plasma membrane (Parekh, , ) and influx of Ca 2+ into the cytosol (Fig.…”
Section: Discussionmentioning
confidence: 97%
“…); and bile acid‐mediated mobilisation of Ca 2+ via IP 3 Rs was also observed in human colonic crypts (Pallagi‐Kunstar et al . ). In PSCs, however, it would appear that the initial release of Ca 2+ from the intracellular stores very quickly leads to depletion of the ER, which triggers opening of store‐operated Ca 2+ entry (SOCE) channels in the plasma membrane (Parekh, , ) and influx of Ca 2+ into the cytosol (Fig.…”
Section: Discussionmentioning
confidence: 97%
“…Furthermore, studies on isolated human colonic epithelial cells have shown that bile acids also inhibit Na + absorption, the main osmotic driving force for colonic fluid absorption. This effect appears to be mediated, at least partly, by Ca 2+ -dependent inhibition of Na + /H + and Cl - /HCO 3 - exchangers in the apical membrane, transport proteins that constitute the pathway for electroneutral Na +  absorption 42, 43…”
Section: Bile Acids and Colonic Fluid And Electrolyte Transportmentioning
confidence: 99%
“…For these experiments, closedloop studies were done in cystic fibrosis mice lacking functional CFTR. Midjejunal and distal colonic closed loops injected with 10 mM CDCA showed a small but significantly greater loop fluid content compared with control loops injected with PBS vehicle, suggesting that mechanisms other than CFTR also play a role in CDCAinduced fluid accumulation, which, based on prior studies, might include inhibition of Na + /H + and Cl 2 /HCO 3 2 exchangers (proabsorptive processes), increased paracellular permeability, or stimulation of mucus secretion (29)(30)(31)(32).…”
Section: Bpo-27 Inhibits Fluid Secretion In Closed Murine Intestinal mentioning
confidence: 99%