کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2481873 1556276 2007 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clonidine accumulation in human neuronal cells
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Clonidine accumulation in human neuronal cells
چکیده انگلیسی

After transport across several epithelial barriers including the blood–brain barrier, clonidine interacts with α2-adrenergic receptors and imidazoline binding sites in the brain. We hypothesized that neuronal cells take up clonidine thereby removing the drug from the extracellular fluid compartment. Uptake of [3H]clonidine into SH-SY5Y neuroblastoma cells was linear for up to 1 min, unaffected by inside directed Na+ or Cl− gradients but strongly inhibited by an outside pH of 6.0. The cells accumulated [3H]clonidine 50–70-fold uphill against a concentration gradient. Unlabeled clonidine, guanabenz, imipramine, diphenhydramine, maprotiline, quinine and the endogenous monoamine phenylethylamine (2 mM) strongly inhibited the [3H]clonidine uptake by 60–95%. Tetraethylammonium, choline and N-methyl-4-phenylpyridinium had no effect. The accumulation at pH 7.5 was saturable with an apparent Michaelis–Menten constant (Kt) of 0.7 mM. We conclude that SH-SY5Y cells not only bind clonidine to extracellular receptors but also take up the drug rapidly by a specific and concentrative mechanism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 32, Issues 4–5, December 2007, Pages 291–295
نویسندگان
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