PROXIMAL COLON--A DISTINCT TRANSPORT EPITHELIUM

我们最近的研究已经描绘了不同的运输参数， 离体兔近端结肠。 这项研究计划的重点是 这些体外转运参数与生物 近端结肠的功能，主要是钠吸收的调节 和短链脂肪酸的分布。 近端结肠的主要离子转运机制是Na+H交换。 我们已经确定了这种吸收过程的几个刺激因素，包括 肾上腺素、糖皮质激素、丙酸盐、清除HCO 3和降低[Na] 在体外培养介质中。 阿米洛利和环磷酸腺苷都能抑制这种作用 各种条件下的运输。 我们已经证明 阿米洛利抑制近端结肠中的氢离子分泌。 的 这项研究旨在研究钠的机制， 吸收，其调节，以及增加和 减少离子运输。 为了研究这个过程，我们将使用尤辛钱伯斯 测量跨上皮转运; pH统计系统，以确定 氢离子分泌;常规微电极测定 细胞内电位差和离子电导的顶端和 基底外侧膜;和pH选择性微电极来测量变化 在细胞内pH值。 近端结肠中主要的管腔阴离子是短链脂肪酸阴离子， acids. 它们在离体离子转运中的作用尚待明确界定; 然而，它们与钠转运关系以及作为一种重要的 热量来源（“结肠补救”）是功能的主要因素 作为胃肠道的离散部分的近端结肠。 我们将在体外研究短链脂肪酸的转运，以确定 是否存在主动转运，与Na吸收的关系， 无论是酸还是离子形式是主要的迁移物质。 Na-H交换剂存在于多种转运上皮细胞中， 一般生理学上的兴趣 近端结肠钠氢交换 具有独特的监管特点，使其研究特别 与理解肠道这一部分的钠吸收有关。 通过 描述近端结肠的特定运输过程，我们将 更好地理解分段异质性的本质 并将深入了解肠道对液体的处理， 电解质，腹泻的病理生理学和可能的作用， 结肠是一个营养器官。

Our recent studies have delineated the distinct transport parameters of rabbit proximal colon in vitro. This research proposal focuses on the relationship of these in vitro transport parameters to the biological functions of the proximal colon, primarily the regulation of Na absorption and the disposition of short-chain fatty acids. The principal ion transport mechanism in proximal colon is Na+H exchange. We have identified several stimuli for this absorptive process including epinephrine, glucocorticoids, proprionate, removal of HCO3 and lowered [Na] in the in vitro bathing media. Both amiloride and cyclic AMP inhibit this transport under various conditions. We have demonstrated amiloride-inhibitible hydrogen ion secretion in the proximal colon. The studies in this grant are designed to investigate the mechanism of Na absorption, its regulation, and the interaction of agents that increase and decrease ion transport. To study this process we will use Ussing chambers to measure transepithelial transport; a pH stat system to determine hydrogen ion secretion; conventional micro-electrodes to determine intracellular potential difference and ionic conductances of the apical and basolateral membranes; and pH-selective microelectrodes to measure changes in intracellular pH. The predominant luminal anions in the proximal colon are short-chain fatty acids. Their role in ion transport in vitro has yet to be clearly defined; however, their relation to Na transport and potential role as a significant source for calories ("colonic salvage") are major factors in the function of the proximal colon as a discrete segment of the gastrointestinal tract. We will study short-chain fatty acid transport in vitro to determine whether active transport is present, the relationship to Na absorption and whether the acid or ionized form is the predominant species transported. Na-H exchangers are found in a wide variety of transport epithelia and are of generalized physiologic interest. Na-H exchange in proximal colon exhibits unique regulatory features that make its study particularly relevant for understanding Na absorption in this part of the gut. By characterizing the specific transport processes of proximal colon, we will achieve a better understanding of the nature of the segmental heterogeneity of the gut and will gain insight into the gut's handling of fluid and electrolytes, the pathophysiology of diarrhea and the possible role of the colon as a nutritive organ.