LEAD EFFECT ON ION TRANSPORT IN FATHEAD GILL

这项建议的目的是评估慢性铅的影响 接触(水基二价铅)钠，钾-三磷酸腺苷酶(NaK- 愚头鱼鳃中ATP酶活性和膜脂的研究 Pimephales proelas.工作假设是低浓度 可溶铅(添加到水族箱水中将对鳃产生深远的影响 阳离子转运机制与二十烷类化合物代谢。这一假设 将在水族馆的实验中进行测试，在这些实验中成年的笨蛋小鱼 将暴露于选定浓度的铅(2-10 ppb，作为铅 硝酸盐)最长可达3个月。校长的长期目标 研究人员正在对这种特殊离子传输进行表征 上皮与哺乳动物的异同 系统。由此获得的信息可能有助于阐明这一机制 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的研究上，包括剂量范围 评估铅对整体健康状况的影响，以及 NAK-ATP-酶活性变化呈浓度依赖性。后来， 首席调查员将对影响进行时间进程研究 铅对鳃ATP酶和氧耗的影响(基础和哇巴因- 可抑制)，以确定鳃上皮的钠泵是否 与其他鳃ATP酶相比，更容易受到铅的抑制。 慢性铅暴露致脂质过氧化损伤的能力 此外，还将使用不同的指数来探索针刺膜 氧化损伤，包括异前列腺素的产生。在最后阶段 项目中，铅对哇巴因抑制氧的影响 消耗、脂质过氧化和二十烷类代谢(细胞色素 P450途径)将与已获得的结果进行比较 大鼠离体近端肾小管的体外研究 饮用水中长期使用的铅。

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.