Nobles M, Diener M, Rummel W
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, F.R.G.
Eur J Pharmacol. 1991 Sep 17;202(2):201-11. doi: 10.1016/0014-2999(91)90295-2.
The heat-stable enterotoxin of E. coli (STa) induced an increase in short-circuit current (Isc) in the rat colon. The maximal increase in Isc was about three times larger in the proximal than the distal colon. The action of STa was mimicked by 8-Br-cyclic GMP. Unidirectional flux measurements revealed that STa decreased Na+ and Cl- absorption in the distal colon, while it decreased Na+ absorption and activated Cl- secretion in the proximal colon. In the distal, but not in the proximal colon, indomethacin inhibited the action of STa and of 8-Br-cyclic GMP. Inhibition by indomethacin could be overcome by addition of prostaglandin E2 or forskolin, but not by addition of a non-hydrolysable analogue of cyclic AMP, suggesting an action of STa on cyclic AMP hydrolysis. Amrinone and trequinsin, two inhibitors of cyclic GMP-inhibited phosphodiesterases, mimicked the action of STa on Isc and inhibited the response to a subsequent administration of the toxin indicating the modulation of a cyclic GMP-inhibited phosphodiesterase by STa in the distal colon. The results give evidence for different intracellular action sites of STa in the two parts of the rat colon.
大肠杆菌的热稳定肠毒素（STa）可使大鼠结肠的短路电流（Isc）增加。Isc的最大增加量在近端结肠比远端结肠大约大三倍。8-溴环鸟苷酸可模拟STa的作用。单向通量测量显示，STa降低了远端结肠中Na⁺和Cl⁻的吸收，而在近端结肠中它降低了Na⁺的吸收并激活了Cl⁻的分泌。在远端结肠而非近端结肠中，吲哚美辛可抑制STa和8-溴环鸟苷酸的作用。添加前列腺素E2或福斯高林可克服吲哚美辛的抑制作用，但添加不可水解的环磷酸腺苷类似物则不能，这表明STa对环磷酸腺苷水解有作用。氨力农和曲喹辛是环鸟苷酸抑制性磷酸二酯酶的两种抑制剂，它们模拟了STa对Isc的作用，并抑制了对随后毒素给药的反应，表明STa在远端结肠中对环鸟苷酸抑制性磷酸二酯酶有调节作用。结果证明了STa在大鼠结肠两部分中的细胞内作用位点不同。
