Mechanism of action of Escherichia coli heat stable enterotoxin in a human colonic cell line.
Mechanism of action of Escherichia coli heat stable enterotoxin in a human colonic cell line.
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大肠杆菌热稳定肠毒素在人结肠细胞系中的作用机制。
DOI：
10.1172/jci113626
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Dharmsathaphorn,K
中科院分区：
文献类型：
--
作者：
Huott,PA;Liu,W;McRoberts,JA;Giannella,RA;Dharmsathaphorn,K
大肠杆菌热稳定性肠毒素（STa）引起的Cl-分泌T84细胞单层的剂量依赖性的方式，只有当应用于顶膜表面，而不是当应用于基底侧表面。cAMP，cGMP，和游离胞质Ca 2+的测量响应于STa表明，cGMP单独介导的Cl-分泌反应。利用Na+，K+-ATP酶泵，Na+，K+，Cl-共转运系统，K+通道和Cl-通道的阻断剂的研究表明，它们都参与了ST a诱导的Cl-分泌过程。结果提示，STa诱导的Cl-分泌反应是在肠毒素与其顶膜受体结合后由cGMP介导的。肠毒素通过增加cGMP，打开基底外侧膜上的K+通道以及顶膜上的Cl-通道。这些离子出口机制的激活，连同Na+、K+、Cl-协同转运蛋白和Na+、K+-ATP酶泵的激活，驱动Cl-通过顶端膜上的Cl-通道出口。
Escherichia coli heat stable enterotoxin (STa) caused Cl- secretion across T84 cell monolayers in a dose-dependent manner only when applied to the apical membrane surface and not when applied to the basolateral surface. Measurement of cAMP, cGMP, and free cytosolic Ca2+ in response to STa suggested that cGMP alone mediated the Cl- secretory response. Studies utilizing blockers of the Na+,K+-ATPase pump, a Na+,K+,Cl- cotransport system, a K+ channel, and a Cl- channel suggest that all of them participate in the Cl- secretory process induced by STa. The results suggest that the Cl- secretory response induced by STa is mediated by cGMP after the enterotoxin binds to its receptor on the apical membrane. The enterotoxin, by increasing cGMP, opens a K+ channel on the basolateral membrane as well as a Cl- channel on the apical membrane. The activation of these ion exit mechanisms, together with activations of the Na+,K+,Cl- cotransporter and the Na+,K+-ATPase pump drives Cl- exit through the Cl- channel on the apical membrane.