Rost Daniel, Mahner Sven, Sugiyama Yuichi, Stremmel Wolfgang
Department of Gastroenterology, University of Heidelberg, 69115 Heidelberg, Germany.
Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G720-6. doi: 10.1152/ajpgi.00318.2001.
Multidrug resistance-associated protein 3 (MRP3; symbol ABCC3), has been shown to mediate ATP-dependent transport of organic anions including 17beta-glucuronosyl estradiol, glucuronosyl bilirubin, monovalent, and sulfated bile salts. MRP3 mRNA expression was reported in rat intestine suggesting a role of MRP3 in the intestinal transport. We examined the expression and localization of MRP3 in rat small and large intestine by RT-PCR, immunofluorescence, and immunoblot analysis. MRP3 was identified in all intestinal segments by RT-PCR. MRP3 expression was low in duodenum and jejunum but markedly increased in ileum and colon. With the use of a rat MRP3 specific antibody, MRP3 was localized to the basolateral domains of enterocytes. Immunofluorescence analysis and immunoblot analysis confirmed a strong expression of rat MRP3 in ileum and colon. In contrast, MRP2 was predominantly expressed in the proximal segments of rat small intestine. Our findings demonstrate a high expression of rat MRP3 in ileum and colon and provide evidence for an involvement of MRP3 in the ATP-dependent transport of organic anions, including bile salts from the enterocyte into blood.
多药耐药相关蛋白3(MRP3;符号为ABCC3)已被证明可介导包括17β-葡萄糖醛酸基雌二醇、葡萄糖醛酸基胆红素、单价和硫酸化胆汁盐在内的有机阴离子的ATP依赖性转运。据报道,MRP3 mRNA在大鼠肠道中表达,提示MRP3在肠道转运中发挥作用。我们通过逆转录聚合酶链反应(RT-PCR)、免疫荧光和免疫印迹分析,研究了MRP3在大鼠小肠和大肠中的表达及定位。通过RT-PCR在所有肠段均鉴定出MRP3。MRP3在十二指肠和空肠中表达较低,但在回肠和结肠中显著增加。使用大鼠MRP3特异性抗体,MRP3定位于肠上皮细胞的基底外侧结构域。免疫荧光分析和免疫印迹分析证实大鼠MRP3在回肠和结肠中强烈表达。相比之下,MRP2主要在大鼠小肠近端段表达。我们的研究结果表明大鼠MRP3在回肠和结肠中高表达,并为MRP3参与包括胆汁盐从肠上皮细胞进入血液的有机阴离子的ATP依赖性转运提供了证据。