کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8514007 1556501 2017 43 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of Proton-Coupled Organic Cation Antiporter in Varenicline Transport at Blood-Brain Barrier of Rats and in Human Brain Capillary Endothelial Cells
ترجمه فارسی عنوان
مشارکت آنتیپورتر کاتیون آلی پروتون با هم در حمل و نقل ونیکلین بر روی مانع خون مغز و در سلول های اندوتلیالی کاپیلاری مغز انسان
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Varenicline is a selective partial α4β2 nicotinic acetylcholine receptor agonist, which is used to help achieve smoking cessation. Here, we investigated varenicline transport at the blood-brain barrier by means of in vivo microdialysis, in situ brain perfusion, and brain efflux index measurements in rats, and in vitro uptake studies in human brain capillary endothelial cells. Microdialysis demonstrated that varenicline is actively transported from blood to brain in rats. Blood-to-brain uptake transport of varenicline, as measured by the in situ brain perfusion technique, was strongly inhibited by diphenhydramine, a potent inhibitor of proton-coupled organic cation (H+/OC) antiporter. However, brain efflux index study showed that brain-to-blood efflux transport of varenicline was not inhibited by diphenhydramine. In human brain capillary endothelial cells, varenicline was taken up time- and concentration-dependently. The uptake was dependent on an oppositely directed proton gradient, but was independent of extracellular sodium and membrane potential. The uptake was inhibited by a metabolic inhibitor, and by substrates of H+/OC antiporter, but not by substrates or inhibitors of OCTs, OCTNs, PMAT, and MATE1, which are known organic cation transporters. The present results suggest that the H+/OC antiporter contributes predominantly to varenicline uptake at the blood-brain barrier.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 9, September 2017, Pages 2576-2582
نویسندگان
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