PROXIMAL COLON--A DISTINCT TRANSPORT EPITHELIUM

我们最近的研究描绘了不同的运输参数 兔离体近端结肠。这项研究建议集中在 这些体外转运参数与生物学特性的关系 近端结肠的功能，主要是钠吸收的调节 以及短链脂肪酸的处置。 近端结肠的离子转运机制主要是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、本酸、去除HCO3和降低[Na] 在体外沐浴介质中。阿米洛利和环磷腺苷都抑制这种作用 各种条件下的运输。我们已经证明了 阿米洛利可抑制近端结肠的氢离子分泌。这个 这项资助的研究旨在研究钠的作用机制。 吸收，它的调节，以及促进和促进 减少离子传输。为了研究这一过程，我们将使用Ussing小室 用来测量跨上皮转运；用pH值统计系统来确定 氢离子分泌.测定的常规微电极 根尖细胞和根尖细胞内电势差和离子电导 基侧膜；以及测量变化的pH选择微电极 在细胞内pH中。 近端结肠中主要的腔内阴离子是短链脂肪。 酸。它们在体外离子转运中的作用尚未明确； 然而，它们与钠转运的关系和潜在的重要作用 卡路里的来源(“结肠保留物”)是影响功能的主要因素 近端结肠作为胃肠道的一个独立部分。 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，与钠吸收和 无论是酸态还是电离态都是主要的输运物种。 Na-H交换器广泛存在于多种运输上皮细胞中，并且 具有普遍的生理兴趣。近端结肠的Na-H交换 展示了独特的监管特征，使其研究尤其 与了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 更好地理解分段异构性的本质 并将深入了解肠道如何处理液体和 电解质、腹泻的病理生理学及其可能的作用 结肠是一种营养器官。

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.