Hydrosoluble Nutrient and Toxicant Absorption by Terrestrial Vertebrates

许多营养物质、天然毒素、人造毒素和药物都是水溶性的（可溶于水）。水溶性化学物质在脊椎动物小肠中的有效运输通常被认为依赖于膜转运蛋白（介导转运），但一些鸟类可以通过细胞间隙（即通过被动的细胞旁通路）有效地运输水溶性化学物质。这项研究将(1)在其他鸟类、哺乳动物和爬行动物中测试这一发现的普遍性，这些动物的体型范围很宽（0.05 kg - 50 kg），(2)测试可能解释水溶性化学物质的细胞旁运输重要性在物种之间差异的机制，以及(3)确定细胞旁途径对毒素的水溶性吸收。生理学、药代动力学和显微镜技术将用于检验这些假设。碳水化合物探针的差异吸收，其大小范围从150 -666道尔顿，将用于评估细胞之间的间隙如何根据分子大小限制运输。两种形式的葡萄糖（D-和l -葡萄糖）吸收的差异将提供介导与被动途径中葡萄糖吸收的相对速率的信息。营养物质（糖）在肠道中对吸收的影响将被确定。将通过光镜和电子显微镜检查肠道组织，以确定可能导致细胞旁吸收变化的结构特征（例如，肠道表面积和相邻细胞间隙紧密连接的密度）。另一项研究将测量两种物种对人造水溶性毒素（除草剂草甘膦）和天然水溶性植物化学物质（花青素）的吸收。草甘膦毒素沿着肠细胞间（而不是穿过）的细胞旁路径的运动将通过放射自显影直接观察。这些研究对脊椎动物生态学、消化生理学、进化生理学和生态毒理学具有重要意义。

Many nutrients, natural toxins, and manmade toxins and drugs are hydrosoluble (soluble in water). Efficient transport of hydrosoluble chemicals across the vertebrate small intestine is generally thought to depend on membrane transport proteins (mediated transport), but some birds can efficiently transport hydrosoluble chemicals through the gaps between cells (i.e., by a passive paracellular pathway). This research will (1) test the generality of this finding in other birds, mammals, and reptiles spanning a broad size range (0.05 kg - 50 kg), (2) test mechanisms that may explain differences among species in the importance of paracellular transport of hydrosoluble chemicals, and (3) determine hydrosoluble absorption of toxins by the paracellular pathway. Physiological, pharmacokinetic, and microscopy techniques will be used to test these hypotheses. The differential absorption of carbohydrate probes, which range in size from 150 -666 Daltons, will be used to assess how the gap between cells restricts transport according to molecular size. Differences in the absorption of two forms of glucose (D- and L-glucose) will provide information about the relative rates of glucose absorption by the mediated versus passive pathways. The effects of a nutrient (sugar) in the gut on absorption will be determined. Intestinal tissues will be examined via light and electron microscopy to characterize structural features (e.g., intestinal surface area and density of tight junctions at the gaps between adjacent cells) that may contribute to variation in paracellular absorption. Another study will measure absorption of a man-made hydrosoluble toxin (the herbicide glyphosate) and a natural hydrosoluble phytochemical (anthocyanin) in two species. Movement of the toxin glyphosate along the paracellular path between (not through) intestinal cells will be directly observed using autoradiography. The proposed studies have important implications for vertebrate ecology, digestive physiology, evolutionary physiology and ecotoxicology.