Guba M, Kuhn M, Forssmann W G, Classen M, Gregor M, Seidler U
First Department of Medicine, Eberhard-Karis-Universität Tübingen, Germany.
Gastroenterology. 1996 Dec;111(6):1558-68. doi: 10.1016/s0016-5085(96)70018-5.
BACKGROUND & AIMS: Guanylin and heat-stable enterotoxin (STa) stimulate intestinal Cl- secretion via activation of the cystic fibrosis transmembrane regulator (CFTR)-encoded Cl- channel. It was speculated that CFTR activation also regulates electrogenic duodenal HCO3- secretion. Therefore, the effect of guanylin/STa and other secretagogues on rat duodenal HCO3- secretion was studied.
The HCO3- secretory rate of in vitro rat proximal duodenum was determined by pH stat titration and paracellular permeability by 3H-mannitol fluxes, bidirectional 36Cl- fluxes were measured, and the short-circuit current (Isc) was recorded.
Luminal guanylin and STa concentration dependently stimulated the HCO3- secretory rate and Isc. Guanylin-stimulated HCO3- secretion was independent of luminal Cl-, inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate, and additive to the HCO3- secretory rate stimulated by glucagon and carbachol but not by the tested adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonists. The ratio of the HCO3- secretory rate/Isc stimulated by the tested guanosine 3',5'-cyclic monophosphate (cGMP)-dependent agonists was markedly higher than the cAMP-dependent agonists. Prostaglandin E2 and 8-bromo-cAMP but not STa/guanylin also transiently increased paracellular permeability.
Guanylin and STa stimulate electrogenic HCO3- secretion in rat duodenum, most likely via CFTR Cl- channel activation, but the different relationship for HCO3- to Isc in cGMP-than in cAMP-stimulated anion secretion suggests a different cellular source and/or signaling pathways.
鸟苷林和热稳定肠毒素（STa）通过激活囊性纤维化跨膜调节因子（CFTR）编码的氯离子通道刺激肠道氯离子分泌。据推测，CFTR激活也调节十二指肠电生性碳酸氢根分泌。因此，研究了鸟苷林/STa及其他促分泌剂对大鼠十二指肠碳酸氢根分泌的影响。
通过pH计滴定法测定体外大鼠近端十二指肠的碳酸氢根分泌速率，通过3H-甘露醇通量测定细胞旁通透性，测量双向36Cl-通量，并记录短路电流（Isc）。
管腔鸟苷林和STa浓度依赖性地刺激碳酸氢根分泌速率和Isc。鸟苷林刺激的碳酸氢根分泌不依赖于管腔氯离子，受氯离子通道阻滞剂5-硝基-2-（3-苯丙基氨基）-苯甲酸抑制，与胰高血糖素和卡巴胆碱刺激的碳酸氢根分泌速率相加，但不受测试的3',5'-环磷酸腺苷（cAMP）依赖性激动剂影响。测试的3',5'-环磷酸鸟苷（cGMP）依赖性激动剂刺激的碳酸氢根分泌速率/Isc比值明显高于cAMP依赖性激动剂。前列腺素E2和8-溴-cAMP而非STa/鸟苷林也短暂增加细胞旁通透性。
鸟苷林和STa刺激大鼠十二指肠电生性碳酸氢根分泌，最可能是通过激活CFTR氯离子通道，但cGMP刺激的阴离子分泌中碳酸氢根与Isc的关系与cAMP刺激的不同，提示细胞来源和/或信号通路不同。
