Ca2+ activates cystic fibrosis transmembrane conductance regulator- and Cl--dependent HCO3- transport in pancreatic duct cells

Wan Namkung, Jin Ah Lee, Wooin Ahn, Won Sun Han, Sung Won Kwon, Duk Sun Ahn, Kyung Hwan Kim, Min Goo Lee

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55 Citations (Scopus)

Abstract

Pancreatic duct cells secrete bicarbonate-rich fluids, which are important for maintaining the patency of pancreatic ductal trees as well as intestinal digestive function. The bulk of bicarbonate secretion in the luminal membrane of duct cells is mediated by a Cl--dependent mechanism (Cl-/HCO3- exchange), and we previously reported that the mechanism is CFTR-dependent and cAMP-activated (Lee, M. G., Choi, J. Y., Luo, X., Strickland, E., Thomas, P. J., and Muallem, S. (1999) J. Biol. Chem. 274, 14670-14677). In the present study, we provide comprehensive evidence that calcium signaling also activates the same CFTR- and Cl--dependent HCO3- transport. ATP and trypsin evoked intracellular calcium signaling in pancreatic duct-derived cells through the activation of purinergic and protease-activated receptors, respectively. Cl-/HCO3- exchange activity was measured by recording pHi in response to [Cl-]o changes of the perfusate. In perfusate containing high concentrations of K+, which blocks Cl- movement through electrogenic or K+-coupled pathways, ATP and trypsin highly stimulated luminal Cl-/HCO3- exchange activity in CAPAN-1 cells expressing wild-type CFTR, but not in CFPAC-1 cells that have defective (ΑF508) CFTR. Notably, adenoviral transfection of wild-type CFTR in CFPAC-1 cells completely restored the stimulatory effect of ATP on luminal Cl-/HCO3- exchange. In addition, the chelation of intracellular calcium by 1,2bis(2-aminophenoxy)ethane-N,N,N,N′-tetraacetic acid (BAPTA) treatment abolished the effect of calcium agonists on luminal Cl-/HCO3- exchange. These results provide a molecular basis for calcium-induced bicarbonate secretion in pancreatic duct cells and highlight the importance of CFTR in epithelial bicarbonate secretion induced by various stimuli.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number1
DOIs
Publication statusPublished - 2003 Jan 3

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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