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Ca2+ Activates Cystic Fibrosis Transmembrane Conductance Regulator- and Cl−-dependent HCOFormula Transport in Pancreatic Duct Cells

Authors
 Wan Namkung  ;  Jin Ah Lee  ;  Min Goo Lee  ;  Kyung Hwan Kim  ;  Duk Sun Ahn  ;  Sung Won Kwon  ;  WonSun Han  ;  Wooin Ahn 
Citation
 Journal of Biological Chemistry, Vol.278(1) : 200-207, 2003 
Journal Title
 Journal of Biological Chemistry 
ISSN
 0021-9258 
Issue Date
2003
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(-)/HCO(3)(-) 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 HCO(3)(-) transport. ATP and trypsin evoked intracellular calcium signaling in pancreatic duct-derived cells through the activation of purinergic and protease-activated receptors, respectively. Cl(-)/HCO(3)(-) exchange activity was measured by recording pH(i) 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(-)/HCO(3)(-) exchange activity in CAPAN-1 cells expressing wild-type CFTR, but not in CFPAC-1 cells that have defective (DeltaF508) CFTR. Notably, adenoviral transfection of wild-type CFTR in CFPAC-1 cells completely restored the stimulatory effect of ATP on luminal Cl(-)/HCO(3)(-) exchange. In addition, the chelation of intracellular calcium by 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid (BAPTA) treatment abolished the effect of calcium agonists on luminal Cl(-)/HCO(3)(-) 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.
Files in This Item:
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DOI
10.1074/jbc.M207199200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
김경환(Kim, Kyung Hwan)
안덕선(Ahn, Duk Sun) ORCID logo https://orcid.org/0000-0001-9351-6951
안우인(Ahn, Woo In)
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
이진아(Lee, Jin Ah)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114667
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