Guanylin strongly stimulates rat duodenal HCO3- secretion: Proposed mechanism and comparison with other secretagogues
Guanylin strongly stimulates rat duodenal HCO3- secretion: Proposed mechanism and comparison with other secretagogues
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DOI：
10.1016/s0016-5085(96)70018-5
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发表时间：
1996-12-01
期刊：
影响因子：
29.4
通讯作者：
Seidler, U
中科院分区：
文献类型：
--
作者：
Guba, M;Kuhn, M;Seidler, U
背景和目标：鸟苷素和热稳定肠毒素（STa）通过激活囊性纤维化跨膜调节因子（CFTR）编码的Cl-通道刺激肠道Cl-分泌，推测CFTR激活也调节产电十二指肠HCO 3-分泌。方法：采用pH滴定法测定离体大鼠近端十二指肠HCO 3-分泌速率，H-3-甘露醇法测定细胞旁通透性，Cl-36（-）双向通量，记录短路电流（Isc）。Guanylin和STa浓度依赖性地刺激HCO_3-分泌速率和Isc，Guanylin刺激的HCO_3-分泌不依赖于Luminal Cl，被Cl通道阻断剂5-硝基-2-（3-苯基丙基氨基）苯甲酸酯，并且添加到由胰高血糖素和卡巴胆碱刺激但不由测试的腺苷3 '，5'-环一磷酸（cAMP）依赖性激动剂刺激的HCO 3分泌速率。受试的环磷酸鸟苷（cGMP）依赖性激动剂刺激的HCO_3分泌速率/Isc的比值明显高于cAMP依赖性激动剂。前列腺素E（2）和8-溴-cAMP，但不是STa/鸟苷素也短暂增加细胞旁通透性。结论：鸟苷素和STa刺激大鼠十二指肠中的生电HCO 3-分泌，最可能是通过CFTR Cl-通道激活，但cGMP-中HCO 3-与Isc的关系与cAMP刺激的阴离子分泌不同，表明不同的细胞来源和/或信号传导途径。
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, Methods: The HCO3- secretory rate of in vitro rat proximal duodenum was determined by pH stat titration and paracellular permeability by H-3-mannitol fluxes, bidirectional Cl-36(-) fluxes were measured, and the short-circuit current (Isc) was recorded, Results: 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 CI 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 E(2) and 8-bromo-cAMP but not STa/guanylin also transiently increased paracellular permeability. Conclusions: Guanylin and STa stimulate electrogenic HCO3- secretion in rat duodenum, most likely vie 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.