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Regulation of ductal bicarbonate transport by intracellular chloride and its role in pancreatic secretion
DC Field | Value | Language |
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dc.contributor.author | 박현우 | - |
dc.date.accessioned | 2015-11-21T07:51:58Z | - |
dc.date.available | 2015-11-21T07:51:58Z | - |
dc.date.issued | 2010 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/125306 | - |
dc.description | Dept. of Medical Science/박사 | - |
dc.description.abstract | [한글] [영문]The exocrine pancreas creates strong alkaline fluid. However, how the human pancreatic duct cells secrete copious amount of bicarbonate (HCO3-) has long been a puzzle for more than a century since it was realized. The present study demonstrates that intracellular Cl- concentration ([Cl-]i)-sensitive mechanisms induces dynamic increase in the CFTR HCO3- permeability which play a pivotal role in the pancreatic HCO3- secretion. In the polarized PANC1 human pancreatic duct cells, CFTR activation rapidly decreased [Cl-]i in response to the luminal Cl- depletion. Interestingly, in human pancreatic tissues, CFTR-positive duct cells co-expressed WNK1, OSR1, and SPAK kinases, which are activated by low [Cl-]i. Notably, the WNK1-mediated OSR1 and SPAK activation by low [Cl-]i strongly increased CFTR HCO3- permeability in the CFTR-transfected HEK 293T, PANC1, and guinea pig pancreatic duct cells making CFTR primarily a HCO3- channel, which is essential for the secretion of pancreatic juice containing HCO3- at a concentration greater than 140 mM. In contrast, OSR1 and SPAK activation inhibited the CFTR-dependent Cl-/HCO3- exchange activity, which may reabsorb HCO3- from the high HCO3--containing pancreatic juice. These results indicate that the [Cl-]i-sensitive activation of WNK1-OSR1/SPAK pathway is the molecular switch to generate HCO3--rich fluids in the human pancreatic ducts. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Regulation of ductal bicarbonate transport by intracellular chloride and its role in pancreatic secretion | - |
dc.title.alternative | 세포 내 염소 이온에 의한 췌장관 중탄산 이온 수송 및 췌액 분비 조절 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Park, Hyun Woo | - |
dc.type.local | Dissertation | - |
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