The antimalarial drug quinine interferes with serotonin biosynthesis and action.
The antimalarial drug quinine interferes with serotonin biosynthesis and action.
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DOI：
10.1038/srep03618
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发表时间：
2014-01-09
影响因子：
4.6
通讯作者：
Avery SV
中科院分区：
文献类型：
--
作者：
Islahudin F;Tindall SM;Mellor IR;Swift K;Christensen HE;Fone KC;Pleass RJ;Ting KN;Avery SV
主要的抗疟药奎宁干扰必需氨基酸色氨酸的摄取，血浆色氨酸水平低的患者易发生奎宁不良反应;其症状与色氨酸耗竭的指征相似。由于色氨酸是神经递质5-羟色胺（5-HT）的前体，在这里我们测试奎宁破坏5-羟色胺功能的假设。奎宁可抑制曲马多宁诱导的酵母和人（SHSY 5 Y）细胞增殖。这种效应的一个可能原因是通过奎宁抑制5-HT受体激活，正如我们在这里观察到的。此外，细胞在与奎宁孵育期间表现出5-羟色胺产生的显著减少。通过测定5-羟色胺生物合成的限速酶色氨酸羟化酶（TPH 2）的活性和动力学，我们发现奎宁在底物色氨酸的存在下竞争性抑制TPH 2。这项研究表明，奎宁破坏血清素的生物合成和功能，为奎宁对哺乳动物细胞的作用提供了重要的新见解。
The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.
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影响因子：
12
作者：
Berman, Jonathan
通讯作者：
Berman, Jonathan
影响因子：
6.6
作者：
Siddiqui, Emad J.;Shabbir, Majid;Mumtaz, Faiz H.
通讯作者：
Mumtaz, Faiz H.
影响因子：
4.7
作者：
Stokes, AH;Xu, YM;Vrana, KE
通讯作者：
Vrana, KE
影响因子：
6.2
作者：
Drozdov, Ignat;Kidd, Mark;Gustafsson, Bjorn I.;Svejda, Bernhard;Joseph, Richard;Pfragner, Roswitha;Modlin, Irvin M.
通讯作者：
Modlin, Irvin M.
影响因子：
3.1
作者：
Clark, CJ;Mackay, GM;Phillips, RS
通讯作者：
Phillips, RS