HEAT-STABLE ENTEROTOXIN OF ESCHERICHIA-COLI - INVITRO EFFECTS ON GUANYLATE CYCLASE ACTIVITY, CYCLIC-GMP CONCENTRATION, AND ION-TRANSPORT IN SMALL-INTESTINE
HEAT-STABLE ENTEROTOXIN OF ESCHERICHIA-COLI - INVITRO EFFECTS ON GUANYLATE CYCLASE ACTIVITY, CYCLIC-GMP CONCENTRATION, AND ION-TRANSPORT IN SMALL-INTESTINE
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DOI：
10.1073/pnas.75.6.2800
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发表时间：
1978-01-01
影响因子：
11.1
通讯作者：
SMITH, PL
中科院分区：
文献类型：
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作者：
FIELD, M;GRAF, LH;SMITH, PL
将部分纯化的热稳定型大肠杆菌肠毒素制剂体外添加到离体家兔回肠粘膜管腔表面，可引起电位差和短路电流的快速持续增加。低至1ng /ml就能产生易于检测的反应。在短路条件下，肠毒素的净Cl-吸收被废除；这种变化是茶碱产生的变化的一半，茶碱刺激净分泌。肠毒素没有改变环AMP浓度，但引起环[c]GMP浓度的持续大幅升高。电反应和核苷酸反应表现出类似的和异常广泛的浓度依赖性，最大效应无法证明。在肠毒素存在和不存在的情况下，茶碱使cGMP浓度升高3倍，表明毒素对cGMP磷酸二酯酶没有影响。鸟苷酸环化酶[GTP焦磷酸酶（环化）；肠毒素刺激肠上皮细胞粗膜组分EC 4.6.1.2的活性达到7倍。刺激鸟苷酸环化酶可能是毒素致泻作用的基础。
A partially purified preparation of the heat-stable enterotoxin of E. coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic[c]GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cGMP concentration 3-fold both in the presence and absence of the enterotoxin, suggesting no effect of the toxin on cGMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. Guanylate cyclase stimulation is probably the basis for the toxin''s diarrheagenic effect.