Bile acids inhibit Na+/H+ exchanger and Cl?/sup>/HCO3 ?/sup> exchanger activities via cellular energy break

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• 作者：é. Pallagi-Kunstár ; K. Farkas ; J. Maléth…
• 关键词：Bile acids ; Colonic epithelial cells ; Ion transporters ; Intracellular Ca2+
• 刊名：Pfl篓鹿gers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：467
• 期：6
• 页码：1277-1290
• 全文大小：1,604 KB
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• 作者单位：é. Pallagi-Kunstár (1)
  K. Farkas (1)
  J. Maléth (1)
  Z. Rakonczay Jr (1)
  F. Nagy (1)
  T. Molnár (1)
  Z. Szepes (1)
  V. Venglovecz (2)
  J. Lonovics (1)
  Z. Rázga (3)
  T. Wittmann (1)
  P. Hegyi (1) (4)
  
  1. Faculty of Medicine, First Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720, Szeged, Hungary
  2. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
  3. Department of Pathology, University of Szeged, Szeged, Hungary
  4. MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

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 diarrhoea. In this study, our aim was to characterise the cellular pathomechanism of bile-induced diarrhoea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na+/H+ exchanger (NHE) and Cl?/sup>/HCO₃ ?/sup> exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhoea, compared to control patients. Acute treatment of colonic crypts with 0.3?mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca2+ elevation. We also showed that chenodeoxycholate induced Ca2+ release from the endoplasmic reticulum and extracellular Ca2+ influx contributing to the Ca2+ elevation. Importantly, our results suggest that the chenodeoxycholate-induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca2+ elevation. We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca2+ overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote the development of diarrhoea.