کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1977708 1061510 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cloning/characterization of the canine organic anion transporting polypeptide 1b4 (Oatp1b4) and classification of the canine OATP/SLCO members
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cloning/characterization of the canine organic anion transporting polypeptide 1b4 (Oatp1b4) and classification of the canine OATP/SLCO members
چکیده انگلیسی

The human liver-specific organic anion transporting polypeptides (OATPs) 1B1 and 1B3 are involved in the elimination of numerous xenobiotics and drugs. Although dogs are frequently used for toxicologic and pharmacokinetic characterization of novel drugs, nothing is known about their OATP1B1/1B3 ortholog. Therefore, we cloned and characterized the first canine organic anion transporting polypeptide from dog liver, termed Oatp1b4. The isolated Oatp1b4 cDNA comprises 3661 base pairs (bp) with an open reading frame of 2076 bp, encoding a 692-amino acid protein with a molecular mass of ∼ 85 kDa. The Oatp1b4 gene is approximately 61 kb long and has a similar organization as the human OATP1B1 and OATP1B3 with 13 exons identical in length. Northern blot analysis shows that Oatp1b4 is predominantly expressed in the liver. Oatp1b4 mediates sodium-independent transport of typical organic anions including bromosulfophthalein (BSP), [D-penicillamine2,5]enkephalin (DPDPE), estradiol-17β-glucuronide (E17βG), estrone-3-sulfate and taurocholate. In addition, Oatp1b4 transports the OATP1B3-specific substrate cholecystokinin octapeptide (CCK-8). Kinetic studies showed that Oatp1b4-mediated E17βG and estrone-3-sulfate transports were monophasic with Km values of 5 ± 1 µM and 33 ± 4 µM, respectively. In conclusion, the cloned canine Oatp1b4 will provide additional molecular basis to further characterize the species difference of the OATP1B family members.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 151, Issue 3, April 2010, Pages 393–399
نویسندگان
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