The role of volume-sensitive Cl- channels in the stimulation of chloride absorption by short-chain fatty acids in the rat colon.

The role of volume-sensitive Cl- channels in the stimulation of chloride absorption by short-chain fatty acids in the rat colon.
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容量敏感的氯离子通道在刺激大鼠结肠中短链脂肪酸吸收氯离子中的作用。

DOI:
10.1111/j.1748-1716.1994.tb09758.x
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发表时间:
1994
期刊:
Acta physiologica Scandinavica
影响因子:
--
通讯作者:
E. Scharrer
E. Scharrer
中科院分区:
--
文献类型:
--
作者:
M. Diener;A. Peter;E. Scharrer

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短链脂肪酸醋酸盐、丙酸盐和丁酸盐在体外诱导大鼠结肠短路电流(Isc)呈浓度依赖性降低。Isc的降低,在远端比在近端结肠中更明显,依赖于Cl-离子的存在,部分依赖于HCO 3-的存在。在远端结肠中,阿米洛利可以抑制Isc的下降,表明Na+/H+交换器的活性是诱导这种反应所必需的。Cl-通道阻滞剂5-硝基-2-(3-苯丙氨基)-苯甲酸酯和脂氧合酶抑制剂去甲二氢愈创木酸可降低Isc。相反,白三烯通路抑制剂或Cl-通道阻滞剂不影响近端结肠的Isc反应。单向通量的测量结果显示,丁酸盐引起的刺激粘膜浆膜通量(FMS)的Na+和Cl-在远端,但只有FNAMS在近端结肠。单向Rb+通量没有改变。Fclms的刺激与短链脂肪酸的代谢程度相关。对于丁酸盐,FClms的增加最明显,对于乙酸盐,FClms的增加较小,并且对于代谢不良的短链脂肪酸异丁酸盐,未观察到FClms的增加。因此,两个因素似乎是负责刺激Cl-吸收的短链脂肪酸在远端结肠:(1)细胞内生产的HCO 3-氧化过程中的短链脂肪酸作为底物的顶端Cl-/HCO 3-交换,和(2)激活体积敏感的基底外侧Cl-通道。
The short-chain fatty acids acetate, propionate and butyrate induced a concentration-dependent decrease in short-circuit current (Isc) of the rat colon in vitro. The decrease in Isc, being more pronounced in the distal than in the proximal colon, was dependent on the presence of Cl- ions and partly on the presence of HCO3-. In the distal colon, the fall in Isc could be inhibited by amiloride, indicating that the activity of the Na+/H+ exchanger is necessary for the induction of this response. The decrease in Isc was diminished by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate, and the lipoxygenase inhibitor, nordihydroguaiaretic acid. In contrast, inhibitors of the leukotriene pathway or a Cl- channel blocker did not affect the Isc response in the proximal colon. Measurements of unidirectional fluxes revealed that butyrate caused a stimulation of the mucosa to serosa fluxes (Fms) of Na+ and Cl- in the distal, but only of FNams in the proximal colon. Unidirectional Rb+ fluxes were not altered. The stimulation of Fclms correlated with the degree of metabolism of the short-chain fatty acid. The increase in FClms was most pronounced for butyrate, smaller for acetate and not observed with the poorly metabolizable short-chain fatty acid, isobutyrate. Consequently, two factors seem to be responsible for the stimulation of Cl- absorption by short-chain fatty acids in the distal colon: (1) the intracellular production of HCO3- during the oxidation of short-chain fatty acids as substrate for the apical Cl-/HCO3- exchanger, and (2) the activation of volume-sensitive basolateral Cl- channels.
DOI: --
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影响因子: --
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DOI: 10.1152/ajpgi.1986.250.6.g781
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影响因子: --
作者:
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通讯作者: Brasitus,TA