LEAD EFFECT ON ION TRANSPORT IN FATHEAD GILL

该提案的目的是评估慢性铅的影响 钠、钾 ATP 酶 (NaK- 黑头鲦鱼鳃中 ATP 酶）活性和膜脂 Pimephales promelas。 工作假设是低浓度 可溶性铅（添加到水族箱水中将深刻影响鳃 阳离子转运机制和类二十烷酸代谢。 这个假设 将在水族馆实验中进行测试，其中成年黑头鲦鱼 将暴露于选定浓度的铅（2-10 ppb，作为铅 硝酸盐）长达 3 个月。 校长的长期目标 研究人员将表征这种特殊的离子传输 上皮细胞与哺乳动物的异同 系统。 由此获得的信息可能有助于阐明该机制 用于人类慢性铅肾病，一种病因不明的疾病。 最初的努力将集中在水族馆研究，包括剂量范围 评估铅对整体健康状况的影响以及 NaK-ATP-ase 变化的浓度依赖性。 随后， 首席研究员将进行效果的时间过程研究 鳃上的 ATP 酶和耗氧量（基础和哇巴因） 可抑制）来确定鳃上皮的钠泵是否被抑制 相对于其他鳃 ATP 酶，更容易受到铅的抑制。 慢性铅暴露引起脂质过氧化损伤的能力 还将利用各种指数来探索鳃膜 氧化损伤，包括异前列腺素的产生。 在最后阶段 该项目中，铅对哇巴因抑制氧的影响 消耗、脂质过氧化和类二十烷酸代谢（细胞色素 鳃上皮中的 P450 通路）将与获得的结果进行比较 用大鼠离体肾近端小管进行离体研究 长期在饮用水中添加铅。

The objective of this proposal is to evaluate the effect of chronic lead exposure (water-borne divalent lead) on sodium, potassium ATP-ase (NaK- ATP-ase) activity and membrane lipids in the gill of the fathead minnow Pimephales promelas. The working hypothesis is that low concentrations of soluble lead (added to aquarium water will profoundly influence gill cation transport mechanisms and eicosanoid metabolism. This hypothesis will be tested in aquarium experiments wherein adult fathead minnows will be exposed to selected concentrations of lead (2-10 ppb, as lead nitrate) for up to 3 months. Long term objectives of the Principal Investigator are to characterize this specialized ion transport epithelium in terms of similarities and differences with mammalian systems. The information thus obtained may shed light on the mechanism for chronic lead nephropathy in humans, a disease with unknown etiology. Initial efforts will focus on aquarium studies, including dose-ranging to assess the effects of lead on overall health status as well as the concentration-dependence of alterations of NaK-ATP-ase. Subsequently, the Principal Investigator will carry out time-course studies of effects of lead on gill ATP-ases and oxygen-consumption (basal and ouabain- inhibitable) to determine whether the sodium pump of gill epithelium is more susceptible to inhibition by lead relative to other gill ATP-ases. The ability of chronic lead exposure to cause lipid peroxidation injury to gill membranes will also be explored, using various indices of oxidative damage, including isoprostane production. In the final stage of the project, the effects of lead on ouabain-inhibitable oxygen consumption, lipid peroxidation and eicosanoid metabolism (cytochrome P450 pathway) in gill epithelium will be compared with those obtained in ex vivo studies with isolated renal proximal tubules from rats chronically administered lead in drinking water.