کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9416263 1292963 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Iptakalim hydrochloride protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Iptakalim hydrochloride protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models
چکیده انگلیسی
Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits KATP channel activation. Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. Chronic exposure of cultured PC12 cells to neurotoxins, such as 6-OHDA, MPP+, or rotenone, decreased overall [3H]-glutamate uptake in a concentration-dependent manner. Pre-treatment using 10 μM Ipt significantly protected cells against neurotoxin-induced glutamate uptake diminishment, and this protection was abolished by the KATP channel blocker glibenclamide (20 μM), suggesting that the protective mechanisms may involve the opening of KATP channels. In 6-OHDA-treated rats (as an in vivo Parkinson's disease model), [3H]-glutamate uptake was significantly lower in synaptosomes isolated from the striatum and cerebral cortex, but not the hippocampus. Pre-conditioning using 10, 50, and 100 μM Ipt significantly restored glutamate uptake impairment and these protections were abolished by blockade of KATP channels. It is concluded that Ipt exhibits substantial protection of cells against neurotoxicity in in vitro and in vivo models. The cellular mechanisms of this protective effect may involve the opening of KATP channels. Collectively, Ipt may serve as a novel and effective drug for PD therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1049, Issue 1, 5 July 2005, Pages 80-88
نویسندگان
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