A primary fish gill cell culture model to assess pharmaceutical uptake and efflux: evidence for passive and facilitated transport.
A primary fish gill cell culture model to assess pharmaceutical uptake and efflux: evidence for passive and facilitated transport.
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DOI：
10.1016/j.aquatox.2014.12.007
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发表时间：
2015-02
影响因子：
4.5
通讯作者：
Bury, Nic R.
中科院分区：
文献类型：
--
作者：
Stott, Lucy C.;Schnell, Sabine;Hogstrand, Christer;Owen, Stewart F.;Bury, Nic R.
鱼鳃的体外模型可用于确定药物穿过鳃的转运。在该模型中，普萘洛尔的摄取具有浓度和pH依赖性，并受抑制剂的影响。某些药物的吸收是通过一个促进过程。鳃是异生物质向水环境转移和从水环境转移的主要场所。为了替换、改进或减少（3Rs）体内吸收研究中使用的大量鱼类，需要进行有效的体外筛选，以模拟硬骨鱼鳃的功能。本研究使用的虹鳟鱼（虹鳟鱼mykiss）的主要鳃细胞培养系统上生长的渗透性插入物，容忍顶端淡水，从而模仿完整的器官，以评估整个鳃的药物的吸收和流出。在介质中的七种药物（普萘洛尔，美托洛尔，阿替洛尔，福莫特罗，特布他林，雷尼替丁和丙咪嗪）的双向运输研究表明，他们跨上皮跨细胞运输。然而，在水中进行的研究表明，普萘洛尔，雷尼替丁和丙咪嗪的吸收增强。没有浓度梯度的浓度平衡条件表明，普萘洛尔和丙咪嗪的摄取比例是通过载体介导的过程。使用普萘洛尔的进一步研究表明，其转运是pH依赖性的，在非常低的环境相关浓度（ng L−1）下，转运偏离线性。在较高浓度下，被动吸收占主导地位。已知的药物转运蛋白抑制剂，西咪替丁，MK 571，环孢素A和奎尼丁抑制普萘洛尔的吸收，而金刚烷胺和维拉帕米没有效果。这表明SLC和ABC药物转运蛋白家族的特定成员参与药物转运。
An in vitro model of the fish gill can be used to determine pharmaceutical transport across the gill. Propranolol uptake across this model is concentration and pH dependent and affected by inhibitors. A component of the uptake of some drugs is via a facilitated process. The gill is the principle site of xenobiotic transfer to and from the aqueous environment. To replace, refine or reduce (3Rs) the large numbers of fish used in in vivo uptake studies an effective in vitro screen is required that mimics the function of the teleost gill. This study uses a rainbow trout (Oncorhynchus mykiss) primary gill cell culture system grown on permeable inserts, which tolerates apical freshwater thus mimicking the intact organ, to assess the uptake and efflux of pharmaceuticals across the gill. Bidirectional transport studies in media of seven pharmaceuticals (propranolol, metoprolol, atenolol, formoterol, terbutaline, ranitidine and imipramine) showed they were transported transcellularly across the epithelium. However, studies conducted in water showed enhanced uptake of propranolol, ranitidine and imipramine. Concentration-equilibrated conditions without a concentration gradient suggested that a proportion of the uptake of propranolol and imipramine is via a carrier-mediated process. Further study using propranolol showed that its transport is pH-dependent and at very low environmentally relevant concentrations (ng L−1), transport deviated from linearity. At higher concentrations, passive uptake dominated. Known inhibitors of drug transport proteins; cimetidine, MK571, cyclosporine A and quinidine inhibited propranolol uptake, whilst amantadine and verapamil were without effect. Together this suggests the involvement of specific members of SLC and ABC drug transporter families in pharmaceutical transport.
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影响因子：
4.5
作者：
Fitzsimmons, PN;Fernandez, JD;Nichols, JW
通讯作者：
Nichols, JW
DOI：
10.1016/j.cbpc.2009.10.009
发表时间：
2010-03-01
影响因子：
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作者：
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通讯作者：
Nalecz-Jawecki, Grzegorz