Basolateral Ca2+-dependent K+-channels play a key role in C1- secretion induced by taurodeoxycholate from colon mucosa

Antonio Moschetta, Piero Portincasa, Lucantonio Debellis, Michele Petruzzelli, Roberta Montelli, Giuseppe Calamita, Pontus Gustavsson, Giuseppe Palasciano

Research output: Contribution to journalArticle

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Abstract

The diarrhea associated with malabsorption of bile salts such as the secondary hydrophobic taurodeoxycholate (TDC) may be partly explained by the TDC-induced increase in colon Cl- secretion. We, therefore, investigated the effects of TDC (0.5-8 mM) on electrical parameters and electrolyte transport of rat proximal colon mucosa mounted in Ussing chambers. Colonic secretion, measured as short circuit current (Isc), progressively increased on mucosal incubation with TDC ranging 0.5-2 mM; up to TDC 2 mM, a spontaneous recovery toward control values with no changes in epithelial resistance (Rt), and lactate dehydrogenase (LDH) release was observed. In contrast, for TDC > 2 mM, Isc increased further and the effect was progressive and associated with a significant decrease in the Rt and increased LDH release, implying a cytolytic effect. Mucosal preincubation with the Cl- channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), fully prevented the precytolytic effect of TDC on Isc. Serosal preincubation with furosemide, a Na+/K+/2Cl- cotransporter inhibitor, significantly reduced TDC-induced increase in Isc. Inhibition of the basolateral Ca2+-dependent K+ channel - rSK4 - with serosal clotrimazole or incubation with mucosal Ca2+-free (EGTA) buffer completely prevented precytolytic TDC-induced increase in Isc. In conclusion, Cl- secretion is activated in colon mucosa by TDC low concentrations; while at higher concentrations, a detergent cytotoxic effect intervenes. Activation of the Ca2+-dependent basolateral K+ pathway, through TDC-induced apical Ca2+ influx, provides the Na+/K+/2Cl- basolateral activation, thereby the driving force for the apical exit of Cl- ions. These findings further enhance the knowledge of the pathogenic mechanisms of diarrhea associated with bile salt malabsorption.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalBiology of the Cell
Volume95
Issue number2
DOIs
StatePublished - Mar 2003

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Taurodeoxycholic Acid
Colon
Mucous Membrane
Bile Acids and Salts
L-Lactate Dehydrogenase
Diarrhea
Clotrimazole
Egtazic Acid
Furosemide
Detergents
Electrolytes

Keywords

  • Bile salts
  • Diarrhea
  • Malabsorption
  • Mucosal transport
  • Ussing

ASJC Scopus subject areas

  • Cell Biology

Cite this

Moschetta, A., Portincasa, P., Debellis, L., Petruzzelli, M., Montelli, R., Calamita, G., ... Palasciano, G. (2003). Basolateral Ca2+-dependent K+-channels play a key role in C1- secretion induced by taurodeoxycholate from colon mucosa. Biology of the Cell, 95(2), 115-122. https://doi.org/10.1016/S0248-4900(03)00011-X

Basolateral Ca2+-dependent K+-channels play a key role in C1- secretion induced by taurodeoxycholate from colon mucosa. / Moschetta, Antonio; Portincasa, Piero; Debellis, Lucantonio; Petruzzelli, Michele; Montelli, Roberta; Calamita, Giuseppe; Gustavsson, Pontus; Palasciano, Giuseppe.

In: Biology of the Cell, Vol. 95, No. 2, 03.2003, p. 115-122.

Research output: Contribution to journalArticle

Moschetta, A, Portincasa, P, Debellis, L, Petruzzelli, M, Montelli, R, Calamita, G, Gustavsson, P & Palasciano, G 2003, 'Basolateral Ca2+-dependent K+-channels play a key role in C1- secretion induced by taurodeoxycholate from colon mucosa', Biology of the Cell, vol. 95, no. 2, pp. 115-122. https://doi.org/10.1016/S0248-4900(03)00011-X
Moschetta, Antonio ; Portincasa, Piero ; Debellis, Lucantonio ; Petruzzelli, Michele ; Montelli, Roberta ; Calamita, Giuseppe ; Gustavsson, Pontus ; Palasciano, Giuseppe. / Basolateral Ca2+-dependent K+-channels play a key role in C1- secretion induced by taurodeoxycholate from colon mucosa. In: Biology of the Cell. 2003 ; Vol. 95, No. 2. pp. 115-122.
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abstract = "The diarrhea associated with malabsorption of bile salts such as the secondary hydrophobic taurodeoxycholate (TDC) may be partly explained by the TDC-induced increase in colon Cl- secretion. We, therefore, investigated the effects of TDC (0.5-8 mM) on electrical parameters and electrolyte transport of rat proximal colon mucosa mounted in Ussing chambers. Colonic secretion, measured as short circuit current (Isc), progressively increased on mucosal incubation with TDC ranging 0.5-2 mM; up to TDC 2 mM, a spontaneous recovery toward control values with no changes in epithelial resistance (Rt), and lactate dehydrogenase (LDH) release was observed. In contrast, for TDC > 2 mM, Isc increased further and the effect was progressive and associated with a significant decrease in the Rt and increased LDH release, implying a cytolytic effect. Mucosal preincubation with the Cl- channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), fully prevented the precytolytic effect of TDC on Isc. Serosal preincubation with furosemide, a Na+/K+/2Cl- cotransporter inhibitor, significantly reduced TDC-induced increase in Isc. Inhibition of the basolateral Ca2+-dependent K+ channel - rSK4 - with serosal clotrimazole or incubation with mucosal Ca2+-free (EGTA) buffer completely prevented precytolytic TDC-induced increase in Isc. In conclusion, Cl- secretion is activated in colon mucosa by TDC low concentrations; while at higher concentrations, a detergent cytotoxic effect intervenes. Activation of the Ca2+-dependent basolateral K+ pathway, through TDC-induced apical Ca2+ influx, provides the Na+/K+/2Cl- basolateral activation, thereby the driving force for the apical exit of Cl- ions. These findings further enhance the knowledge of the pathogenic mechanisms of diarrhea associated with bile salt malabsorption.",
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