Three distinct mechanisms of HCO3- secretion in rat distal colon.
Three distinct mechanisms of HCO3- secretion in rat distal colon.
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DOI：
10.1152/ajpcell.00474.2003
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发表时间：
2004-09
期刊：
影响因子：
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通讯作者：
S. Vidyasagar;V. Rajendran;H. Binder
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文献类型：
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作者：
S. Vidyasagar;V. Rajendran;H. Binder
HCO(3)（-）分泌在哺乳动物结肠中早已被发现，但尚未被很好地表征。尽管大多数关于结肠HCO(3)（-）分泌的研究都揭示了管腔Cl（-）依赖性的证据，提示顶端膜Cl(-)/HCO(3)（-）交换的作用，但直接检查大鼠远端结肠离体隐窝中HCO(3)（-）分泌并未发现Cl（-）依赖性的HCO(3)（-）分泌，但确实发现了camp诱导的Cl（-）非依赖性的HCO(3)（-）分泌。因此，研究开始确定离体结肠粘膜中HCO(3)（-）分泌的特征，以确定表面细胞和隐窝细胞中HCO(3)（-）的分泌。用pH值测定法测定大鼠结肠远端剥离肌肉层和浆膜层后的HCO(3)（-）分泌。基础HCO(3)（-）分泌（5.6 +/- 0.03 microeq.h(-1)）。通过去除腔内Cl（-）或槽内HCO(3)（-）来消除cm(-2)；这种Cl（-）依赖性的HCO(3)（-）分泌也被100 microM DIDS （0.5 +/- 0.03 microeq.h(-1)）抑制。cm(-2))，而不是5-硝基-3-（3-苯基丙基-氨基）苯甲酸（NPPB），一种Cl（-）通道阻滞剂。8-Bromo-cAMP诱导Cl（-）非依赖性HCO(3)（-）分泌(并抑制Cl（-）依赖性HCO（3)（-）分泌），NPPB和CFTR阻滞剂格列本脲可抑制HCO(3)（-）分泌，但DIDS不能。异丁酸是一种代谢不良的短链脂肪酸（SCFA），也能诱导一种不依赖Cl（-）、dids不敏感、可饱和的HCO(3)（-）分泌，这种分泌不受NPPB的抑制。确定了三种不同的HCO（3)（-）分泌机制：1）与顶膜Cl（-)/HCO（3)（-）交换相关的Cl（-）依赖性分泌，2）由于顶膜阴离子通道导致的camp诱导分泌，以及3）与顶膜SCFA/HCO(3)（-）交换相关的SCFA依赖性分泌。
HCO(3)(-) secretion has long been recognized in the mammalian colon, but it has not been well characterized. Although most studies of colonic HCO(3)(-) secretion have revealed evidence of lumen Cl(-) dependence, suggesting a role for apical membrane Cl(-)/HCO(3)(-) exchange, direct examination of HCO(3)(-) secretion in isolated crypt from rat distal colon did not identify Cl(-)-dependent HCO(3)(-) secretion but did reveal cAMP-induced, Cl(-)-independent HCO(3)(-) secretion. Studies were therefore initiated to determine the characteristics of HCO(3)(-) secretion in isolated colonic mucosa to identify HCO(3)(-) secretion in both surface and crypt cells. HCO(3)(-) secretion was measured in rat distal colonic mucosa stripped of muscular and serosal layers by using a pH stat technique. Basal HCO(3)(-) secretion (5.6 +/- 0.03 microeq.h(-1).cm(-2)) was abolished by removal of either lumen Cl(-) or bath HCO(3)(-); this Cl(-)-dependent HCO(3)(-) secretion was also inhibited by 100 microM DIDS (0.5 +/- 0.03 microeq.h(-1).cm(-2)) but not by 5-nitro-3-(3-phenylpropyl-amino)benzoic acid (NPPB), a Cl(-) channel blocker. 8-Bromo-cAMP induced Cl(-)-independent HCO(3)(-) secretion (and also inhibited Cl(-)-dependent HCO(3)(-) secretion), which was inhibited by NPPB and by glibenclamide, a CFTR blocker, but not by DIDS. Isobutyrate, a poorly metabolized short-chain fatty acid (SCFA), also induced a Cl(-)-independent, DIDS-insensitive, saturable HCO(3)(-) secretion that was not inhibited by NPPB. Three distinct HCO(3)(-) secretory mechanisms were identified: 1) Cl(-)-dependent secretion associated with apical membrane Cl(-)/HCO(3)(-) exchange, 2) cAMP-induced secretion that was a result of an apical membrane anion channel, and 3) SCFA-dependent secretion associated with an apical membrane SCFA/HCO(3)(-) exchange.