Recent studies in perfused livers and isolated hepatocytes indicate that ursodeoxycholic acid-induced HCO3-rich hypercholeresis originates at the ductule/duct level. The bile duct epithelium may be involved in bile alkalinization by passively reabsorbing the protonated unconjugated ursodeoxycholic acid, by directly secreting in response to an ursodeoxycholic acid-induced increase in acid/base transporter activity or by taking up UDCA- in exchange for a base equivalent. To investigate these processes in more detail, we studied the effects of ursodeoxycholic acid on intracellular pH in SK-ChA-1, a well-differentiated human cholangiocarcinoma cell line similar to bile duct epithelium in terms of intracellular pH regulatory mechanisms and morphological markers. Intracellular pH changes were monitored with a microfluorimetric setup using the fluorescent indicator 2'-7'-bis(2-carboxyethyl)-5,6,carboxy fluorescein. Administration of 50 to 1,000 mumol/L UDCA in the absence of HCO3 caused dose-dependent intracellular acidification (intracellular pH = -0.13 +/- 0.03 pH/U after 500 mumol/L ursodeoxycholic acid). Acidification was not prevented by preincubation of cells with 0.5 mmol/L 4,4-diisothiocyanatostilbene-2,2,-disulfonic acid (DIDS) for 30 min or by furosemide administration (1 mmol/L), thus ruling out the stimulation of Cl/HCO3 exchange or the presence of an ursodeoxycholic acid/base exchange. Ursodeoxycholic acid also acidified human fibroblasts, a cell type with no transport capability for ursodeoxycholic acid. In addition, direct measurement of the activities of the three major acid/base transporters in Sk-ChA-1 cells (Na+/H+ exchange, sodium-dependent and sodium-independent Cl/HCO3 exchange) failed to show significative differences between cells treated with 500 mumol/L UDCA and controls

Strazzabosco, M., Poci, C., Spirlí, C., Sartori, L., Knuth, A., Crepaldi, G. (1994). Effect of ursodeoxycholic acid on intracellular pH in a bile duct epithelium-like cell line. HEPATOLOGY, 19(1), 145-154 [10.1002/hep.1840190124].

Effect of ursodeoxycholic acid on intracellular pH in a bile duct epithelium-like cell line

Strazzabosco, M;
1994

Abstract

Recent studies in perfused livers and isolated hepatocytes indicate that ursodeoxycholic acid-induced HCO3-rich hypercholeresis originates at the ductule/duct level. The bile duct epithelium may be involved in bile alkalinization by passively reabsorbing the protonated unconjugated ursodeoxycholic acid, by directly secreting in response to an ursodeoxycholic acid-induced increase in acid/base transporter activity or by taking up UDCA- in exchange for a base equivalent. To investigate these processes in more detail, we studied the effects of ursodeoxycholic acid on intracellular pH in SK-ChA-1, a well-differentiated human cholangiocarcinoma cell line similar to bile duct epithelium in terms of intracellular pH regulatory mechanisms and morphological markers. Intracellular pH changes were monitored with a microfluorimetric setup using the fluorescent indicator 2'-7'-bis(2-carboxyethyl)-5,6,carboxy fluorescein. Administration of 50 to 1,000 mumol/L UDCA in the absence of HCO3 caused dose-dependent intracellular acidification (intracellular pH = -0.13 +/- 0.03 pH/U after 500 mumol/L ursodeoxycholic acid). Acidification was not prevented by preincubation of cells with 0.5 mmol/L 4,4-diisothiocyanatostilbene-2,2,-disulfonic acid (DIDS) for 30 min or by furosemide administration (1 mmol/L), thus ruling out the stimulation of Cl/HCO3 exchange or the presence of an ursodeoxycholic acid/base exchange. Ursodeoxycholic acid also acidified human fibroblasts, a cell type with no transport capability for ursodeoxycholic acid. In addition, direct measurement of the activities of the three major acid/base transporters in Sk-ChA-1 cells (Na+/H+ exchange, sodium-dependent and sodium-independent Cl/HCO3 exchange) failed to show significative differences between cells treated with 500 mumol/L UDCA and controls
Articolo in rivista - Articolo scientifico
ursodeoxycholic acid, UDCA, liver, cholangiocytes, bile ducts
English
1994
19
1
145
154
none
Strazzabosco, M., Poci, C., Spirlí, C., Sartori, L., Knuth, A., Crepaldi, G. (1994). Effect of ursodeoxycholic acid on intracellular pH in a bile duct epithelium-like cell line. HEPATOLOGY, 19(1), 145-154 [10.1002/hep.1840190124].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/8215
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