MK‐801 blocks monoamine transporters expressed in HEK cells

FEBS Letters

Shimada, Shoichi¹  Nishimura, Mitsuhiro²  Tohyama, Masaya²  Sato, Kohji⁴  Schloss, Patrick³  Okada, Tomoya² 

[1] Department of Anatomy, Nagoya City University Medical School Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan;Department of Anatomy and Neuroscience, Osaka University Medical School, Yamadaoka 2-2, Suita, Osaka 565, Japan;Biochemistry Department, University of Dublin, Trinity College, Dublin 2, Ireland;Department of Anatomy, Ehime University School of Medicine, Shigenobu, Ehime 791-02, Japan

关键词: MK-801;    Norepinephrine transporter;    Dopamine transporter;    Serotonin transporter;    N-Methyl-d-aspartate receptor;    Human embryonic kidney cell;    MK-801;    (+)-5-methyl-10;    11-dihydro-5H-dibenzo[a;    d]cyclohepten-5;    10-imine maleate;    CPP;    3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid;    HEK cell;    human embryonic kidney cell;   

DOI  :  10.1016/S0014-5793(98)00126-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

(+)-MK-801 is known to be a specific non-competitive antagonist of N-methyl-d-aspartate (NMDA) receptors. However, besides having an anticonvulsant effect, this compound possesses a central sympathomimetic effect and an anxiolytic-like action, raising the possibility that (+)-MK-801 might affect monoamine uptake systems. To elucidate this possibility, we investigated the effects of (+)-MK-801 on monoamine transporters expressed in HEK cells. (+)-MK-801 significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner and the inhibitions were competitive with respect to monoamines. The K _i values of (+)-MK-801 on the norepinephrine, dopamine and serotonin transporters were 3.2 μM, 40 μM and 43 μM, respectively. In addition, (−)-MK-801, a less potent antagonist of NMDA receptors, also inhibited monoamine transporters with a similar potency as that of (+)-MK-801. These results clearly indicate that MK-801, a non-competitive antagonist of NMDA receptors, competitively inhibits monoamine transporters without stereoselectivity.

【 授权许可】

Unknown