Stimulation of HCO3– Secretion across Cystic Fibrosis Pancreatic Duct Cells by Extracellular ATP

Stimulation of HCO3– Secretion across Cystic Fibrosis Pancreatic Duct Cells by Extracellular ATP
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细胞外 ATP 刺激囊性纤维化胰管细胞分泌 HCO3

DOI：
10.1159/000014555
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发表时间：
1998
期刊：
Neurosignals
影响因子：
--
通讯作者：
H. Chan
H. Chan
中科院分区：
--
文献类型：
--
作者：
C. Cheung;X. Wang;H. Chan

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已有研究表明，细胞外ATP能够激活Ca<sup>2+</sup>依赖性Cl<sup>-</sup>通道，这可能是克服囊性纤维化（CF）时cAMP依赖性胰腺导管HCO<sub>3</sub><sup>-</sup>分泌缺陷的重要途径。本研究进一步探讨了细胞外ATP对CF胰管细胞（CFPAC-1）分泌HCO<sub>3</sub><sup>-</sup>的影响。细胞在培养板插入物中生长，这使得pH微电极能够进入顶端隔室。测定了细胞外ATP刺激后根尖pH值的变化，作为HCO<sub>3</sub><sup>-</sup>分泌的指标。ATP诱导的顶端pH值的快速增加，达到一个平台，平均pH值单位为0.3高于未受刺激的细胞中测得的。ATP的作用呈浓度依赖性。ATP诱导的pH变化可被顶端加入Cl<sup>-</sup>通道阻断剂所阻断，表明顶端Cl<sup>-</sup>通道的激活对胰管细胞分泌HCO<sub>3</sub><sup>-</sup>至关重要。结合以前的发现，本研究表明，CF胰管细胞的HCO<sub>3</sub><sup>-</sup>分泌可能是通过cAMP非依赖性途径由细胞外ATP刺激的。
Previous studies have demonstrated that extracellular ATP is able to activate Ca<sup>2+</sup>-dependent Cl<sup>–</sup> channels which may be important in circumventing the defective cAMP-dependent pancreatic ductal HCO<sub>3</sub><sup>–</sup> secretion in cystic fibrosis (CF). The present study further investigated the effect of extracellular ATP on the stimulation of HCO<sub>3</sub><sup>–</sup> secretion across CF pancreatic duct cells (CFPAC-1). Cells were grown in culture plate inserts which enabled the access of a pH microelectrode to the apical compartment. Changes in apical pH upon stimulation by extracellular ATP, as an indication of HCO<sub>3</sub><sup>–</sup> secretion, were measured. ATP induced a rapid increase in apical pH, which reached a plateau with an averaged pH unit of 0.3 higher than that measured in unstimulated cells. The effect of ATP was concentration dependent. The ATP-induced change in pH could be blocked by apical addition of Cl<sup>–</sup> channel blockers, indicating that activation of apical Cl<sup>–</sup> channel is vital for HCO<sub>3</sub><sup>–</sup> secretion by the pancreatic duct cells. Together with the previous finding, the present study suggests that HCO<sub>3</sub><sup>–</sup> secretion may be stimulated in CF pancreatic duct cells by extracellular ATP via a cAMP-independent pathway.
A CYSTIC-FIBROSIS PANCREATIC ADENOCARCINOMA CELL-LINE
DOI： 10.1073/pnas.87.10.4012
发表时间： 1990-05-01
期刊： PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子： 11.1
作者：
SCHOUMACHER, RA;RAM, J;FRIZZELL, RA
通讯作者： FRIZZELL, RA