کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5840398 1560481 2016 40 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Organic cation rhodamines for screening organic cation transporters in early stages of drug development
ترجمه فارسی عنوان
راتامین های کاتیونی آلی برای غربالگری حمل کنندگان کاتیون های آلی در مراحل اولیه توسعه دارو
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
چکیده انگلیسی
The aim of this study was to investigate the suitability of rhodamine-123, rhodamine-6G and rhodamine B as non-radioactive probes for characterizing organic cation transporters in respiratory cells. Fluorescent characteristics of the compounds were validated under standard in vitro drug transport conditions (buffers, pH, and light). Uptake/transport kinetics and intracellular accumulation of the compounds were investigated. Uptake/transport mechanisms were investigated by comparing the effect of pH, temperature, concentration, polarity, OCTs/OCTNs inhibitors/substrates, and metabolic inhibitors on the cationic dyes uptake in Calu-3 cells. Fluorescence stability and intensity of the compounds were altered by buffer composition, light, and pH. Uptake of the dyes was concentration-, temperature- and pH-dependent. OCTs/OCTNs inhibitors significantly reduced intracellular accumulation of the compounds. Whereas rhodamine-B uptake was sodium-dependent, pH had no effect on rhodamine-123 and rhodamine-6G uptake. Transport of the dyes across the cells was polarized: (AP → BL > BL → AP transport) and saturable: {Vmax = 14.08 ± 2.074, Km = 1821 ± 380.4 (rhodamine-B); Vmax = 6.555 ± 0.4106, Km = 1353 ± 130.4 (rhodamine-123) and Vmax = 0.3056 ± 0.01402, Km = 702.9 ± 60.97 (rhodamine-6G)}. The dyes were co-localized with MitoTracker®, the mitochondrial marker. Cationic rhodamines, especially rhodamine-B and rhodamine- 6G can be used as organic cation transporter substrates in respiratory cells. During such studies, buffer selection, pH and light exposure should be taken into consideration.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmacological and Toxicological Methods - Volume 82, November–December 2016, Pages 9-19
نویسندگان
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