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Inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in murine mastocytoma P815 cells

机译：四氢罂粟碱对小鼠肥大细胞瘤P815细胞血清素生物合成的抑制作用

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摘要

The inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in serotonin-producing murine mastocytoma P815 cells were investigated. Tetrahydropapaverine at concentration ranges of 5-20 muM decreased serotonin content in a concentration-dependent manner in P815 cells and showed 42.1% inhibition of serotonin content at 5.0 muM at 24 hr. The value of 50% inhibitory concentration, IC50, of tetrahydropapaverine was 6.2 muM. Under these conditions, tryptophan hydroxylase (EC 1.14.16.4, TPH) was inhibited for 24-36 hr after treatment with tetrahydropapaverine in P815 cells (49.1% inhibition at 7.5 muM). However, aromatic L-amino acid decarboxylase activity was not affected by tetrahydropapaverine. In addition, tetrahydropapaverine inhibited the activity of TPH, prepared from the P815 cells (P815-TPH), with the IC50 value of 5.7 muM. Tetrahydropapaverine un-competitively inhibited P815-TPH with the substrate L-tryptophan, and non-competitively with the cofactor DL-6-methyl-5,6,7,8-tetrahydropteridin. The K-i value of tetrahydropapaverine with L-tryptophan was 10.1 muM. These data indicate that tetrahydropapaverine leads to a decrease in serotonin content by the inhibition of TPH activity in P815 cells. (C) 2004 Elsevier Inc. All rights reserved.
机译：研究了四氢罂粟碱对产生5-羟色胺的鼠肥大细胞瘤P815细胞中5-羟色胺生物合成的抑制作用。在P815细胞中，浓度为5-20μM的四氢罂粟碱以浓度依赖的方式降低了血清素的含量，并在24小时显示5.0μM的血清素含量抑制了42.1％。四氢罂粟碱的50％抑制浓度IC50值为6.2μM。在这些条件下，色氨酸羟化酶（EC 1.14.16.4，TPH）在P815细胞中用四氢罂粟碱处理后被抑制24-36小时（在7.5μM时抑制49.1％）。但是，芳香氢L-氨基酸脱羧酶活性不受四氢罂粟碱的影响。此外，四氢罂粟碱抑制了由P815细胞（P815-TPH）制备的TPH的活性，IC50值为5.7μM。四氢罂粟碱与底物L-色氨酸竞争性抑制P815-TPH，与辅因子DL-6-甲基-5,6,7,8-四氢蝶呤抑制竞争。四氢罂粟碱与L-色氨酸的K-i值为10.1μM。这些数据表明四氢罂粟碱通过抑制P815细胞中的TPH活性而导致血清素含量降低。 （C）2004 Elsevier Inc.保留所有权利。

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