Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2)
Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2)
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DOI：
10.1124/jpet.102.044404
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发表时间：
2003-02-01
影响因子：
3.5
通讯作者：
Schömig, E
中科院分区：
文献类型：
--
作者：
Gründemann, DG;Hahne, C;Schömig, E
阿格马汀最近受到了相当大的关注。现有证据表明，胍丁胺作为一种神经递质发挥作用，并通过诱导抗酶抑制细胞增殖。由于其正电荷，胍丁胺不会通过简单的扩散而明显地穿过细胞膜。事实上，所有的生理模型都需要质膜中的通道或转运蛋白来灭活或非胞吐释放胍丁胺。然而，目前还没有从分子水平上确定胍丁胺的转运机制。本研究检测了人和大鼠的非神经元性单胺转运蛋白--有机阳离子转运蛋白(OCT)1、OCT2和神经元外单胺转运蛋白(EMT)(基因符号SLC22A1-A3)，并在293细胞中稳定表达，以研究[H-3]胍丁胺的转运蛋白。我们的结果表明，OCT2和EMT，而不是OCT1，有效地转运了胍丁胺。结构同系物腐胺不被接受为底物。胍丁胺通过EMT和OCT2的摄取是饱和的，K-m值为1~2 mm。OCT1的亲和力降低了10倍。载体介导的胍丁胺外流在反式刺激实验中被记录下来。随着pH的升高，胍丁胺的摄取量显著增加。因此，只有胍丁胺的单电荷物种才被接受为底物。综上所述，必须同时考虑EMT和OCT2来控制大鼠和人体内的胍丁胺水平。
Agmatine has received considerable attention recently. Available evidence suggests that agmatine functions as a neurotransmitter and inhibits, via induction of antizyme, cellular proliferation. Because of its positive charge, agmatine will not appreciably cross cellular membranes by simple diffusion. Indeed, all physiological models require a channel or transporter protein in the plasma membrane to effect inactivation or non-exocytotic release of agmatine. However, a transport mechanism for agmatine has not been identified on a molecular level so far. In the present study, the non-neuronal monoamine transporters, organic cation transporter (OCT) 1, OCT2, and extraneuronal monoamine transporter (EMT) (gene symbols SLC22A1-A3), both from human and rat, were examined, stably expressed in 293 cells, for [H-3] agmatine transport. Our results indicate that OCT2 and EMT, but not OCT1, efficiently translocate agmatine. The structural homolog putrescine was not accepted as substrate. Uptake of agmatine via EMT and OCT2 was saturable, with K-m values of 1 to 2 mM. The affinity of OCT1 was 10-fold lower. Carrier-mediated efflux of agmatine was documented in a trans-stimulation experiment. Finally, uptake of agmatine increased dramatically with increasing pH. Thus, only the singly charged species of agmatine is accepted as substrate. In conclusion, both EMT and OCT2 must be considered for the control of agmatine levels in rat and human.