کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2485497 1114356 2011 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional characterization of Rat Plasma Membrane Monoamine Transporter in the Blood–Brain and Blood–Cerebrospinal Fluid Barriers
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Functional characterization of Rat Plasma Membrane Monoamine Transporter in the Blood–Brain and Blood–Cerebrospinal Fluid Barriers
چکیده انگلیسی

This study investigated the expression and functional roles of rat plasma membrane monoamine transporter (rPMAT) in the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier by using in vitro brain barrier model cells (TR-BBB13 and TR-CSFB3 cells) and multiple in vivo experimental techniques. Quantitative reverse transcription-polymerase chain reaction analysis showed relatively high expression of rPMAT mRNA in TR-BBB13 and TR-CSFB3 cells. 1-Methyl-4-phenylpyridinium (MPP+) was transported into rPMAT-expressing cells in a sodium-independent manner. [3H]MPP+ was taken up concentration dependently by TR-BBB13 and TR-CSFB3 cells with Km values similar to that of rPMAT-expressing cells. [3H]MPP+ transports into these cells were markedly inhibited by serotonin, dopamine, and cationic drugs. rPMAT small interfering RNA (siRNA) significantly suppressed the [3H]MPP+ uptake by TR-BBB13 cells. Intracerebrally injected [3H]MPP+ was eliminated from the brain parenchymal region, whereas brain [3H]MPP+ uptake did not increase with time during in situ brain perfusion, suggesting that the brain-to-blood transport across the BBB predominates over the blood-to-brain transport. Brain microdialysis studies revealed that the elimination across the BBB was significantly decreased by coperfusion of unlabelled MPP+, serotonin, or dopamine. [3H]MPP+ was also eliminated from the CSF. These findings suggest that PMAT in brain barriers functions as the brain-to-blood transporter to regulate brain concentrations of organic cations including monoamines and cationic neurotoxins. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3924–3938, 2011

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 9, September 2011, Pages 3924–3938
نویسندگان
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