کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2479115 1113424 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional Pleiotropy of Organic Anion Transporting Polypeptide OATP2B1 Due to Multiple Binding Sites
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Functional Pleiotropy of Organic Anion Transporting Polypeptide OATP2B1 Due to Multiple Binding Sites
چکیده انگلیسی

Summary:The purpose of this study was to examine whether the presence of multiple binding sites can explain the pleiotropy of substrate recognition by OATP2B1, using Xenopus oocytes expressing OATP2B1. OATP2B1-mediated uptake of estrone-3-sulfate apparently exhibited biphasic saturation kinetics, with Km values of 0.10 ± 0.05 and 29.9 ± 12.1 μΜ and Vmax values of 14.1 ± 6.4 and 995 ± 273 fmol/min/oocyte for high- and low-affinity sites, respectively. Contribution analysis revealed that transport of estrone-3-sulfate mediated by high- and low-affinity sites on OATP2B1 could be evaluated at the concentrations of 0.005 and 50 μΜ, respectively. pH-dependence study of OATP2B1-mediated estrones-sulfate uptake suggested that high- and low-affinity sites show different pH sensitivity. When the inhibitory effect of 12 compounds on estrone-3-sulfate uptake by high- and low-affinity sites on OATP2B1 was examined, 4 compounds appeared to be inhibitors of the high-affinity site on OATP2B1. Two other compounds appeared to be inhibitors for the low-affinity site and four others were inhibitory at both sites. These results indicated the presence of multiple binding sites on OATP2B1 with different affinity for drugs. Accordingly, it is likely that drug-drug and drug-beverage interactions occur only when two drugs share the same binding site on OATP2B1.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 27, Issue 3, 2012, Pages 360–364
نویسندگان
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