Guandalini S, Rao M C, Smith P L, Field M
Am J Physiol. 1982 Jul;243(1):G36-41. doi: 10.1152/ajpgi.1982.243.1.G36.
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.
致泻性大肠杆菌菌株已被证明能产生一种热稳定肠毒素（ST），该毒素可模拟鸟苷酸环化酶，增加短路电流（Isc），并抑制肠道中氯离子的主动吸收。在兔回肠中，离子转运效应比环磷酸腺苷（cAMP）相关激动剂所产生的效应小。由于ST可能是一种选择性环磷酸鸟苷（cGMP）激动剂，我们进一步探讨了其在兔回肠中的作用模式。ST抑制钠和氯的净吸收。ST还抑制与茶碱抑制相同比例的氯离子通过刷状缘的内流。在最大剂量下，ST和8-溴-cGMP对Isc的作用几乎相等且无相加效应，约为8-溴-cAMP所产生效应的66%。ST使黏膜cGMP浓度增加了16倍，而作为分泌抑制剂的肾上腺素仅使cGMP浓度增加了30%。这不足以改变离子转运，因为使cGMP浓度增加100%的ST剂量未能改变氯离子通量。此外，肾上腺素在分离的肠细胞中并未增加cGMP浓度。我们得出结论：1）cGMP介导ST对离子转运的作用；2）尽管ST和cAMP相关激动剂具有相同的抗吸收作用，但ST在刺激氯离子电分泌方面效果较差。
