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Parathyroid hormone increases CFTR expression and function in Caco-2 intestinal epithelial cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Mar 12; Vol. 523 (3), pp. 816-821. Date of Electronic Publication: 2020 Jan 15. - Publication Year :
- 2020
-
Abstract
- Parathyroid hormone (PTH) enhances cystic fibrosis transmembrane conductance regulator (CFTR)-mediated anion secretion by the human intestinal epithelial cell line Caco-2. With the patch-clamp and Ussing chamber techniques, we investigated how PTH stimulates CFTR activity in Caco-2 cells. Cell-attached recordings revealed that PTH stimulated the opening of CFTR-like channels, while impedance analysis demonstrated that PTH increased apical membrane capacitance, a measure of membrane surface area. Using ion substitution experiments, the PTH-stimulated increase in short-circuit current (I <subscript>sc</subscript> ), a measure of transepithelial ion transport, was demonstrated to be Cl <superscript>-</superscript> - and HCO <subscript>3</subscript> <superscript>-</superscript> -dependent. However, the PTH-stimulated increase in I <subscript>sc</subscript> was unaffected by the carbonic anhydrase inhibitor acetazolamide, but partially blocked by the intermediate-conductance Ca <superscript>2+</superscript> -activated K <superscript>+</superscript> channel (IKCa) inhibitor clotrimazole. TRAM-34, a related IKCa inhibitor, failed to directly inhibit CFTR Cl <superscript>-</superscript> channels in cell-free membrane patches, excluding its action on CFTR. In conclusion, PTH enhances CFTR-mediated anion secretion by Caco-2 monolayers by increasing the expression and function of CFTR in the apical membrane and IKCa activity in the basolateral membrane.<br />Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Anions metabolism
Caco-2 Cells
Cystic Fibrosis Transmembrane Conductance Regulator analysis
Cystic Fibrosis Transmembrane Conductance Regulator genetics
Humans
Intestinal Mucosa cytology
Ion Transport
Up-Regulation
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Intestinal Mucosa metabolism
Parathyroid Hormone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 523
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 31954520
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.12.106