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Am J Physiol Cell Physiol. 2011 Jul;301(1):C137-49. doi: 10.1152/ajpcell.00001.2011. Epub 2011 Mar 9.

Parathyroid hormone (PTH) rapidly enhances CFTR-mediated HCO₃⁻ secretion in intestinal epithelium-like Caco-2 monolayer: a novel ion regulatory action of PTH.

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Consortium for Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand.


Besides being a Ca²-regulating hormone, parathyroid hormone (PTH) has also been shown to regulate epithelial transport of certain ions, such as Cl, HCO₃, and Na, particularly in the kidney. Although the intestinal epithelium also expressed PTH receptors, little was known regarding its mechanism in the regulation of intestinal ion transport. We investigated the ion regulatory role of PTH in intestinal epithelium-like Caco-2 monolayer by Ussing chamber technique and alternating current impedance spectroscopy. It was found that Caco-2 cells rapidly responded to PTH within 1 min by increasing apical HCO₃- secretion. CFTR served as the principal route for PTH-stimulated apical HCOV efflux, which was abolished by various CFTR inhibitors, namely, NPPB, glycine hydrazide-101 (GlyH-101), and CFTRinh-172, as well as by small interfering RNA against CFTR. Concurrently, the plasma membrane resistance was decreased with no changes in the plasma membrane capacitance or paracellular permeability. HCOV was probably supplied by basolateral uptake via the electrogenic Na⁺-HCO₃⁻ cotransporter and by methazolamide-sensitive carbonic anhydrase, while the resulting intracellular H⁺ might be extruded by both apical and basolateral Na/H exchangers. Furthermore, the PTH-stimulated HCO₃-secretion was markedly reduced by protein kinase A (PKA) inhibitor (PKI 14-22 amide) and phosphoinositide 3-kinase (PI3K) inhibitors (wortmannin and LY-294002), but not by intracellular Ca²⁺ chelator (BAPTA-AM) or protein kinase C inhibitor (GF-109203X). In conclusion, the present study provided evidence that PTH directly and rapidly stimulated apical HCO₃- secretion through CFTR in PKA- and PI3K-dependent manner, which was a novel noncalciotropic, ion regulatory action of PTH in the intestinal epithelium.

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