Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake.

摘要: The human organic cation transporter 1 (OCT1) is a polyspecific involved in the uptake of positively charged and neutral small molecules liver. To date, few endogenous compounds have been identified as OCT1 substrates; more importantly, effect drugs on substrate transport has not examined. In this study, we established monoamine neurotransmitters substrates for OCT1, specifically characterizing serotonin embryonic kidney 293 cells. Kinetic analysis yielded Km 197 micomolar Vmax 561 pmol/mg protein/minute serotonin. Furthermore, demonstrated that was inhibited by diphenhydramine, fluoxetine, imatinib, verapamil, with IC50 values low micromolar range. These results were recapitulated primary hepatocytes, suggesting plays significant role hepatic elimination xenobiotics may alter result interactions at level.