Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2)

• DOI: 10.1016/s0014-5793(99)00979-5
• Publication Date: 2002-07-25T17:52:28Z
• Authors: Takeshi Kawabe; Zhe-Sheng Chen; Morimasa Wada; Takeshi Uchiumi; Mayumi Ono; Shin-ichi Akiyama; Michihiko Kuwano
• Keywords: Leukotriene C4; P-glycoprotein

We established stable human canalicular multispecific organic anion transporter ( cMOAT/MRP2 ) cDNA transfectants, CHO/cMOAT from non‐polarized Chinese hamster ovary (CHO)‐K1 and LLC/cMOAT polarized pig kidney epithelial LLC‐PK1. Human cMOAT was mainly localized in the plasma membrane of apical LLC/cMOAT. The ATP‐dependent uptake leukotriene C 4 (LTC into vesicles enhanced compared with empty vector transfectants. K m values were 0.24 μM for LTC 175 ATP. Drug sensitivity to vincristine cisplatin transfectants decreased, but not etoposide. Cellular accumulation inhibited by exogenous administration or cisplatin, that Moreover, this inhibition more presence glutathione. These consequences indicate drug resistance appears be modulated through transport agents, possibly direct indirect association