cGMP modulation of ileal ion transport: in vitro effects of Escherichia coli heat-stable enterotoxin.
cGMP modulation of ileal ion transport: in vitro effects of Escherichia coli heat-stable enterotoxin.
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回肠离子转运的 cGMP 调节：大肠杆菌热稳定肠毒素的体外作用。
DOI：
10.1152/ajpgi.1982.243.1.g36
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Field,M
中科院分区：
文献类型：
--
作者：
Guandalini,S;Rao,MC;Smith,PL;Field,M
致泻大肠杆菌菌株已被证明会产生一种热稳定肠毒素（ST），该毒素可刺激鸟苷酸环化酶、增加短路电流（Isc）并抑制肠道中的活性氯吸收。在兔回肠中，离子转运效应小于cAMP相关激动剂产生的效应。由于ST可能是一种选择性cGMP激动剂，我们进一步探讨了其在兔回肠中的作用方式。ST抑制净Na和净Cl吸收。ST也抑制茶碱抑制的相同分数的Cl流入刷状缘。在最大剂量下，ST和8-Br-cGMP（8-Br-cGMP）对Isc的影响几乎相等，非累加效应约为8-Br-cAMP产生的Isc的66%。ST增加粘膜cGMP浓度16倍，而肾上腺素，分泌抑制剂，增加cGMP浓度仅30%。这不足以改变离子转运，因为增加cGMP浓度100%的ST剂量未能改变Cl通量。此外，肾上腺素没有增加cGMP浓度在分离的肠上皮细胞。我们的结论是：1）cGMP介导ST对离子转运的作用，2）虽然ST和cAMP相关激动剂具有相同的抗吸收作用，ST在刺激产电性Cl分泌方面效果较差。
Diarrheagenic strains of Escherichia coli have been shown to produce a heat-stable enterotoxin (ST) that simulates guanylate cyclase, increases short-circuit current (Isc), and inhibits active Cl absorption in the intestine. In rabbit ileum, the ion transport effects are smaller than those produced by cAMP-related agonists. Because ST may be a selective cGMP agonist, we further explored its mode of action in rabbit ileum. ST inhibits net Na and net Cl absorption. ST also inhibits the same fraction of Cl influx across the brush border that theophylline inhibits. At maximal doses, ST and 8-bromo-cGMP (8-Br-cGMP) had nearly equal, nonadditive effects of Isc that were about 66% of that produced by 8-Br-cAMP. ST increased mucosal cGMP concentration 16-fold, whereas epinephrine, an inhibitor of secretion, increased cGMP concentration by only 30%. This is insufficient to alter ion transport because doses of ST that increased cGMP concentration by 100% failed to alter Cl fluxes. Furthermore, epinephrine did not increase cGMP concentration in isolated enterocytes. We conclude that 1) cGMP mediates ST effects on ion transport, and 2) although ST and cAMP-related agonists have the same antiabsorptive effects, ST is less effective in stimulating electrogenic Cl secretion.