兔结肠短链脂肪酸的体外吸收

Short-chain fatty acid absorption in rabbit colon in vitro.

作者信息

Sellin J H, DeSoignie R

机构信息

Department of Internal Medicine, University of Texas Medical School, Houston.

出版信息

Gastroenterology. 1990 Sep;99(3):676-83. doi: 10.1016/0016-5085(90)90954-y.

DOI:10.1016/0016-5085(90)90954-y

PMID:2379774

Abstract

Short-chain fatty acids are the predominant luminal anion in the colon and are generally absorbed rapidly in vivo. However, the mechanisms of in vitro transport of short-chain fatty acids have not been fully delineated. Therefore, we examined [14C]propionate fluxes in rabbit proximal colon under short-circuit conditions. There was minimal metabolism of propionate (less than 10%), permitting accurate flux measurements using a radioisotopic tracer. In a 20 mmol/L propionate Ringer's solution at pH 7.4, there was a significant rate of propionate secretion (-0.58 +/- 0.08 microEq.cm-2.h-1). Decreasing pH to 6.8 by decreasing bicarbonate concentration in the bathing medium resulted in increases in unidirectional fluxes but no change in net transport. Reversal of propionate secretion to propionate absorption was elicited by HEPES substitution for bicarbonate at pH 6.8 or by serosal addition of epinephrine, which increases apical Na(+)-H+ exchange in this epithelium. Propionate absorption was blocked by both amiloride, an Na(+)-H+ exchange inhibitor, and ouabain. Under basal conditions, there was a concentration-dependent increase in basal unidirectional propionate fluxes with no change in net transport as the concentration of propionate increased from 10 to 60 mmol/L. In contrast, a concentration-dependent saturation of epinephrine-stimulated propionate absorption was apparent. Transepithelial propionate gradients did not yield a significant diffusion potential. These results suggest that, in rabbit proximal colon, (a) there is bidirectional diffusion of propionate, most probably in the protonated rather than the ionized form; (b) a component of propionate transport is active and linked to electroneutral Na+ absorption through apical Na(+)-H+ exchange; and (c) changes in composition of the fluid bathing the proximal colon in vitro may significantly alter both rates and direction of short-chain fatty acid transport. Regulation of transcellular active transport may play an important role in colonic short-chain fatty acid conservation.

摘要

短链脂肪酸是结肠腔内的主要阴离子，在体内通常迅速被吸收。然而，短链脂肪酸的体外转运机制尚未完全阐明。因此，我们在短路条件下检测了兔近端结肠中[¹⁴C]丙酸盐的通量。丙酸盐的代谢极少（低于10%），这使得使用放射性同位素示踪剂进行准确的通量测量成为可能。在pH 7.4的20 mmol/L丙酸盐林格氏液中，丙酸盐分泌速率显著（-0.58±0.08微当量·厘米⁻²·小时⁻¹）。通过降低浴液介质中的碳酸氢盐浓度将pH降至6.8，导致单向通量增加，但净转运无变化。在pH 6.8时用HEPES替代碳酸氢盐或在浆膜侧添加肾上腺素（可增加该上皮细胞顶端的Na⁺-H⁺交换），可使丙酸盐分泌逆转至丙酸盐吸收。丙酸盐吸收被Na⁺-H⁺交换抑制剂氨氯吡脒和哇巴因阻断。在基础条件下，随着丙酸盐浓度从10 mmol/L增加到60 mmol/L，基础单向丙酸盐通量呈浓度依赖性增加，而净转运无变化。相比之下，肾上腺素刺激的丙酸盐吸收明显呈现浓度依赖性饱和。跨上皮丙酸盐梯度未产生显著的扩散电位。这些结果表明，在兔近端结肠中，（a）丙酸盐存在双向扩散，最可能以质子化而非离子化形式；（b）丙酸盐转运的一个组成部分是主动的，并通过顶端Na⁺-H⁺交换与电中性Na⁺吸收相关联；（c）体外近端结肠浴液成分的变化可能显著改变短链脂肪酸转运的速率和方向。跨细胞主动转运的调节可能在结肠短链脂肪酸的保存中起重要作用。