ALDOSTERONE INDUCED COLONIC H+ SECRETION & VESICLES

这位研究者以前曾证明，结肠氯化钠 吸收被醛固酮或地塞米松显著改变。 这是 并伴有结肠内新的管腔膜囊泡的出现 而不是地塞米松治疗的大鼠。 醛固酮 诱导的小泡在外观和位置上与我们认为的 参与乌龟膀胱H+分泌， 大鼠髓集合管的闰细胞，并可能在 胃壁细胞 初步的pH统计实验表明，大鼠 远端结肠分泌H+，即H+分泌超过乳酸产生， H+分泌既有钠依赖性，也有非钠依赖性 成分，并且已知产生细胞内酸化的策略 刺激H+分泌。 在这些研究的同时， 研究表明，囊泡数量减少，并向 在CO2暴露产生的细胞内酸化后， 有可能融合囊泡膜和加入H+泵 到顶端膜。 吖啶橙子的实验表明， 在大鼠结肠中存在酸性囊泡。 因此，有可能 醛固酮激活大鼠远端结肠中H+分泌的新形式， 一个涉及膜囊泡和胞吐融合。 本研究者 计划进一步表征H+分泌在远端结肠段， 未处理的大鼠和用醛固酮或地塞米松处理的大鼠。 这将通过离子置换研究和使用 特异性抑制剂 在这些研究的同时，定量 形态测定和荧光探针将被用来确定 醛固酮诱导的酸性囊泡的分布，并检查 对增强或抑制H+分泌的药剂的反应。 具体 长期目标是研究这一系统的引入， 醛固酮，其调节一旦到位，和的作用， 细胞骨架在其调控中的作用。 这些研究对一些人来说很重要。 原因 H+分泌和离子转运均不受胞吐调节 在肠上皮细胞中已经证实了融合。 审查 这些醛固酮诱导的膜囊泡的功能可能 提供这方面的新信息。 这些研究都是高度相关的 我们对肠道离子转运的理解 盐皮质激素和糖皮质激素类固醇。

This investigator has previously demonstrated that colonic sodium chloride absorption is markedly altered by aldosterone or dexamethasone. This was accompanied by the appearance of new luminal membrane vesicles in colon from aldosterone but not from dexamethasone treated rats. The aldosterone induced vesicles are similar in appearance and location to vesicles thought to be involved in H+ secretion in turtle urinary bladder, in the intercalated cell of rat medullary collecting duct, and possibly in the gastric parietal cell. Preliminary pH stat experiments indicate that rat distal colon secretes H+, that H+ secretion exceeds lactate production, that H+ secretion has both sodium-dependent and sodium-independent components, and that maneuvers known to produce intracellular acidification stimulate H+ secretion. In parallel with these studies, morphologic studies demonstrate a reduction in vesicle number and migration toward the lumen after intracellular acidification produced by CO2 exposure consistent with the possibility of fusion of vesicle membrane and addition of H+ pumps to the apical membrane. Experiments with acridine orange have shown that there are acidic vesicles in rat colon. Thus, it is possible that aldosterone activates a new form of H+ secretion in the rat distal colon, one involving membrane vesicles and exocytotic fusion. This investigator plans to further characterize H+ secretion in distal colon segments from untreated rats and from rats treated with aldosterone or dexamethasone. This will be accomplished by ion substitution studies and by the use of specific inhibitors. In parallel with these studies, quantitative morphometry and fluorescent probes will be utilized to determine the distribution of aldosterone induced acidic vesicles and to examine the response to agents which augment or inhibit H+ secretion. The specific long-term objectives are to study the induction of this system by aldosterone, its regulation once it is in place, and the role of the cytoskeleton in its regulation. These studies are important for several reasons. Neither H+ secretion nor ion transport regulated by exocytotic fusion have been demonstrated in intestinal epithelia. Examination of the function of these aldosterone induced membrane vesicles is likely to provide new information in this regard. These studies are highly relevant to our understanding of intestinal ion transport and the modification thereof by mineralocorticoid and glucorticoid steroids.