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Functional Role of Basolateral ClC-2 Channels in the Regulation of Duodenal Anion Secretion in Mice.
- Source :
-
Digestive diseases and sciences [Dig Dis Sci] 2019 Sep; Vol. 64 (9), pp. 2527-2537. Date of Electronic Publication: 2019 Mar 14. - Publication Year :
- 2019
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Abstract
- Background: Although ClC-2 channels are important in colonic Cl <superscript>-</superscript> secretion, it is unclear about their roles in small intestinal anion secretion. Therefore, we sought to examine whether ClC-2 channels play important roles in anion secretion, particularly duodenal bicarbonate secretion (DBS).<br />Methods: Duodenal mucosae from mice were stripped of seromuscular layers and mounted in Ussing chambers. Both duodenal short-circuit current (I <subscript>sc</subscript> ) and HCO <subscript>3</subscript> <superscript>-</superscript> secretion in vitro were simultaneously recorded. DBS in vivo was measured by a CO <subscript>2</subscript> -sensitive electrode.<br />Results: Lubiprostone, a selective ClC-2 activator, concentration-dependently increased both duodenal I <subscript>sc</subscript> and DBS only when applied basolaterally, but not when applied apically. Removal of extracellular Cl <superscript>-</superscript> abolished lubiprostone-induced duodenal I <subscript>sc</subscript> , but did not alter HCO <subscript>3</subscript> <superscript>-</superscript> secretion even in the presence of DIDS, a Cl <superscript>-</superscript> /HCO <subscript>3</subscript> <superscript>-</superscript> exchanger inhibitor. However, further addition of glibenclamide, a CFTR channel blocker, abolished lubiprostone-evoked HCO <subscript>3</subscript> <superscript>-</superscript> secretion. Moreover, lubiprostone-induced HCO <subscript>3</subscript> <superscript>-</superscript> secretion was impaired in CFTR <superscript>-/-</superscript> mice compared to wild-type littermates. Luminal perfusion of duodenal lumen with lubiprostone did not alter basal DBS in vivo, but lubiprostone (i.p.) was able to induce DBS, which was also significantly inhibited by Cd <superscript>2+</superscript> , a ClC-2 channel blocker. [Ca <superscript>2+</superscript> ] <subscript>cyt</subscript> level, Ca <superscript>2+</superscript> -activated K <superscript>+</superscript> channel- and cAMP-mediated duodenal I <subscript>sc</subscript> , and HCO <subscript>3</subscript> <superscript>-</superscript> secretion were unchanged by lubiprostone.<br />Conclusions: We have provided the first evidence for the novel functional role of basolateral ClC-2 channels in the regulation of duodenal anion secretion.
- Subjects :
- Animals
CLC-2 Chloride Channels
Chloride Channel Agonists pharmacology
Chloride Channels antagonists & inhibitors
Cystic Fibrosis Transmembrane Conductance Regulator deficiency
Cystic Fibrosis Transmembrane Conductance Regulator genetics
Duodenum drug effects
Intestinal Mucosa drug effects
Lubiprostone pharmacology
Mice
Mice, Knockout
Chloride Channels physiology
Duodenum metabolism
Intestinal Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2568
- Volume :
- 64
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Digestive diseases and sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30874987
- Full Text :
- https://doi.org/10.1007/s10620-019-05578-7