DeSoignie R, Sellin J H
Department of Internal Medicine, University of Texas Medical School at Houston.
Gastroenterology. 1994 Aug;107(2):347-56. doi: 10.1016/0016-5085(94)90158-9.
BACKGROUND/AIMS: Because regulation of intracellular pH (pHi) is critical to basic cell functions, most cells have evolved mechanisms to closely regulate intracellular acid-base balance. Short-chain fatty acids (SCFAs), the predominant luminal anion in the colon, acidify the cell interior in several cell systems, but their effect on their "natural target," the colonocytes, has not been examined thoroughly.
We monitored the pHi response to a model SCFA, propionate, in isolated cells and epithelial sheets from rabbit proximal colon loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein.
SCFAs induced a characteristic pHi response curve in colonocytes: an immediate acidification and a recovery phase returning to baseline in 100-200 seconds. Acidification was altered by increasing concentrations of SCFAs, by increasing SCFA chain length, extracellular osmolarity, and intracellular pH, and finally, Na+ removal. The recovery phase was slowed by amiloride and 4-alpha-OH cinnamate, an inhibitor of proton-monocarboxylate cotransport.
Physiological concentrations of SCFAs have profound effects on intracellular pH. Simple diffusion of the SCFA may not explain the complexities of propionate-induced protonated acidification; the pH recovery phase may involve multiple processes including Na(+)-H+ exchange and H(+)-SCFA cotransport. Luminal constituents such as SCFAs may have significant effects on the intracellular pH and function of colonocytes.
背景/目的：由于细胞内pH（pHi）的调节对基本细胞功能至关重要，大多数细胞已进化出密切调节细胞内酸碱平衡的机制。短链脂肪酸（SCFAs）是结肠腔中的主要阴离子，在多种细胞系统中可使细胞内部酸化，但其对其“天然靶标”结肠上皮细胞的影响尚未得到充分研究。
我们使用负载pH敏感染料2',7'-双（2-羧乙基）-5-（和-6）羧基荧光素的兔近端结肠分离细胞和上皮片，监测pHi对模型短链脂肪酸丙酸的反应。
短链脂肪酸在结肠上皮细胞中诱导出特征性的pHi反应曲线：立即酸化，然后在100 - 200秒内恢复至基线的恢复阶段。酸化程度因短链脂肪酸浓度增加、链长增加、细胞外渗透压、细胞内pH的变化以及最终的钠离子去除而改变。氨氯吡咪和4-α-羟基肉桂酸（一种质子-单羧酸共转运抑制剂）可减缓恢复阶段。
生理浓度的短链脂肪酸对细胞内pH有深远影响。短链脂肪酸的简单扩散可能无法解释丙酸诱导的质子化酸化的复杂性；pH恢复阶段可能涉及多个过程，包括钠氢交换和氢-短链脂肪酸共转运。像短链脂肪酸这样的腔内成分可能对结肠上皮细胞的细胞内pH和功能有显著影响。
