有机阴离子转运多肽
有机阴离子转运蛋白1
有机阳离子转运蛋白
化学
运输机
有机阴离子
排泄
体内
转运蛋白
ATP结合盒运输机
多药耐药蛋白2
生物化学
体外
药理学
生物
基因
离子
生物技术
有机化学
作者
Dallas Bednarczyk,Carri Boiselle
出处
期刊:Xenobiotica
[Informa]
日期:2015-09-18
卷期号:46 (5): 457-466
被引量:64
标识
DOI:10.3109/00498254.2015.1085111
摘要
1. Organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 are polyspecific transporters that mediate the transport of organic acids into hepatocytes. Inactivating mutations of both OATP1B1 and OATP1B3 alleles lead to Rotor syndrome, a disease characterized by coproporphyrinuria, an elevated urinary excretion of coproporphyrins I and III. It was hypothesized that transport of coproporphyrins I and III was mediated by OATP1B1 and OATP1B3.2. This hypothesis was tested using cells transfected with OATP1B1 and OATP1B3. OATP1B-mediated transport of coproporphyrin was time-dependent and concentration-dependent. OATP1B1-mediated transport of coproporphyrins I and III (Km = 0.13 and 0.22 µM, respectively), as did OATP1B3 (Km = 3.25 and 4.61 µM, respectively). The OATP1B-mediated transport of each coproporphyrin was inhibited by rifampicin.3. The specificity of coproporphyrin transport was also investigated where OATP2B1 demonstrated meaningful transport of coproporphyrin III (Km = 0.31 µM), while OCT1, OCT2, OAT1, OAT3 and NTCP were negative for coproporphyrin transport.4. The identification of coproporphyrins as OATP substrates in vitro more clearly defines the role of OATPs in the hepatic disposition and renal excretion of coproporphyrins I and III and provides compelling evidence for future in vivo exploration of coproporphyrins as biomarkers of OATP activity.
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