کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484292 | 1114305 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chloroquine and Hydroxychloroquine Are Novel Inhibitors of Human Organic Anion Transporting Polypeptide 1A2
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کلمات کلیدی
PAHSLCsE3SHCQRPECCK-8cholecystokinin octapeptide - cholecystokinin oktapeptideMPP+ - MPP +estrone-3-sulfate - استرون -3 سولفاتretinal pigment epithelium - اپیتلیوم رنگدانه شبکیهInhibition - بازداریDrug interaction - تعاملات داروییAll-trans-retinol - تمام ترانس رتینولOrganic anion-transporting polypeptide transporters - حمل و نقل پلی پپتید های آنیونی ارگانیزمorganic anion transporters - حملونقل آنیونی آلیhydroxychloroquine - هیدروکسی کلروکینOrganic cation transporters - کانتینرهای ارگانیکChloroquine - کلروکین
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used to treat malaria and inflammatory diseases, long-term usage of which often causes severe side effects, especially retinopathy. Solute carrier transporters (SLCs) are important proteins responsible for the cellular uptake of endogenous and exogenous substances. Inhibitors competing with transporter substrates for SLCs often results in unfavorable toxicities and unsatisfactory therapeutic outcomes. We investigated the inhibitory effect of CQ and HCQ on substrate uptake mediated through a range of important SLC transporters in overexpressing human embryonic kidney (HEK293) cells. Our data revealed that both CQ and HCQ potently inhibit the uptake activity of organic anion transporting polypeptide 1A2 (OATP1A2). We recently reported OATP1A2 to be expressed in human retinal pigment epithelium (RPE), where it mediates cellular uptake of all-trans-retinol (atROL), a key step in the classical visual cycle. In this study, we demonstrate that CQ and HCQ could markedly impair atROL uptake in OATP1A2-expressing HEK293 cells and more importantly, in primary human RPE cells. Our study shows that CQ and HCQ are novel inhibitors of OATP1A2 and significantly impair OATP1A2-mediated substrate uptake, particularly transport of atROL into the RPE. This effect may compromise the function of the classic visual cycle leading to vision impairment and contribute to the retinopathy observed clinically in patients using CQ or HCQ.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 884-890
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 2, February 2016, Pages 884-890
نویسندگان
Chenghao Xu, Ling Zhu, Ting Chan, Xiaoxi Lu, Weiyong Shen, Michele C. Madigan, Mark C. Gillies, Fanfan Zhou,