Diener M, Peter A, Scharrer E
Institute for Veterinary Physiology, University of Zürich, Switzerland.
Acta Physiol Scand. 1994 Jul;151(3):385-94. doi: 10.1111/j.1748-1716.1994.tb09758.x.
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.
短链脂肪酸乙酸盐、丙酸盐和丁酸盐可使体外培养的大鼠结肠短路电流（Isc）呈浓度依赖性降低。Isc的降低在结肠远端比近端更明显，其依赖于Cl-离子的存在，部分依赖于HCO3-的存在。在结肠远端，Isc的下降可被氨氯吡咪抑制，这表明Na+/H+交换体的活性对于诱导此反应是必需的。Isc的降低被Cl-通道阻滞剂5-硝基-2-（3-苯丙基氨基）-苯甲酸盐和脂氧合酶抑制剂去甲二氢愈创木酸减弱。相反，白三烯途径抑制剂或Cl-通道阻滞剂不影响近端结肠的Isc反应。单向通量测量显示，丁酸盐可刺激远端结肠中Na+和Cl-从黏膜到浆膜的通量（Fms），但仅刺激近端结肠中FNa的通量。单向Rb+通量未改变。FClms的刺激与短链脂肪酸的代谢程度相关。FClms的增加在丁酸盐时最为明显，在乙酸盐时较小，而在难代谢的短链脂肪酸异丁酸盐时未观察到。因此，似乎有两个因素导致远端结肠中短链脂肪酸对Cl-吸收的刺激：（1）短链脂肪酸氧化过程中细胞内产生HCO3-作为顶端Cl-/HCO3-交换体的底物，以及（2）容积敏感性基底外侧Cl-通道的激活。
