Fujita T, Yamada H, Fukuzumi M, Nishimaki A, Yamamoto A, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Life Sci. 1997;60(4-5):307-13. doi: 10.1016/s0024-3205(96)00631-5.
In this study, we report the efflux mechanism of calcein, an organic anion, mediated by a multidrug resistance-associated protein (MRP)-like protein in the intestinal mucosal membrane. The transport of calcein from the mucosal to serosal side was decreased dose-dependently and was significantly lower than that of the opposite direction. In addition, its transport was increased in the presence of metabolic inhibitors and probenecid. Furthermore, the efflux of calcein from the intestinal cell membrane, which was preloaded with calcein acetoxymethyl ester, was predominantly observed in the mucosal side rather than in the serosal side. Its efflux to the mucosal side was inhibited by the metabolic inhibitors and probenecid, not by verapamil which is a P-glycoprotein substrate. These results indicated that the transport of calcein and possibly other organic anions across the intestinal membrane may be regulated by the MRP-like protein, but not P-glycoprotein.
在本研究中，我们报告了一种有机阴离子——钙黄绿素，在肠黏膜膜中由一种多药耐药相关蛋白（MRP）样蛋白介导的外排机制。钙黄绿素从黏膜侧向浆膜侧的转运呈剂量依赖性降低，且显著低于相反方向的转运。此外，在存在代谢抑制剂和丙磺舒的情况下其转运增加。此外，预先加载了钙黄绿素乙酰氧基甲酯的肠细胞膜中钙黄绿素的外排主要在黏膜侧而非浆膜侧观察到。其向黏膜侧的外排受到代谢抑制剂和丙磺舒的抑制，而非维拉帕米（一种P-糖蛋白底物）的抑制。这些结果表明，钙黄绿素以及可能其他有机阴离子跨肠膜的转运可能受MRP样蛋白调节，而非P-糖蛋白调节。
