Sulfation of opioid drugs by human cytosolic sulfotransferases: metabolic labeling study and enzymatic analysis.
Sulfation of opioid drugs by human cytosolic sulfotransferases: metabolic labeling study and enzymatic analysis.
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DOI：
10.1016/j.ejps.2014.05.003
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发表时间：
2014-10-01
影响因子：
4.6
通讯作者：
Liu, Ming-Cheh
中科院分区：
文献类型：
--
作者：
Kurogi, Katsuhisa;Chepak, Andriy;Hanrahan, Michael T.;Liu, Ming-Yih;Sakakibara, Yoichi;Suiko, Masahito;Liu, Ming-Cheh
目前的研究旨在检测八种阿片类药物（吗啡、氢吗啡酮、羟吗啡酮、布托啡诺、纳布啡、左啡诺、纳洛啡和纳曲酮）在 HepG2 人肝癌细胞和人体器官样本（肺、肝、肾和小肠）中的硫酸化情况，并确定导致其硫酸化的人类 SULT。在八种阿片类药物中的每一种存在下，用[35S]硫酸盐代谢标记的HepG2细胞的废培养基的分析显示了相应的[35S]硫酸化衍生物的生成和释放。八种阿片类药物中的五种（氢吗啡酮、羟吗啡酮、布托啡诺、纳洛啡和纳曲酮）在 HepG2 细胞中的硫酸化程度似乎比其他三种药物（吗啡、纳布啡和左啡诺）更强。在人肺、肝脏、小肠和肾脏的细胞质或 S9 部分中检测到对阿片类药物的不同硫酸化活性，其中肝脏样本的活性最高。使用 11 种已知的人类 SULT 和动力学实验进行的系统分析表明，SULT1A1 是羟吗啡酮、纳布啡、纳洛啡和纳曲酮硫酸化的主要负责 SULT，SULT1A3 负责吗啡和氢吗啡酮的硫酸化，SULT2A1 负责布托啡诺和左啡诺的硫酸化。总的来说，获得的结果表明硫酸化可能在测试的阿片类药物的体内代谢中发挥重要作用。
The current study was designed to examine the sulfation of eight opioid drugs, morphine, hydromorphone, oxymorphone, butorphanol, nalbuphine, levorphanol, nalorphine, and naltrexone, in HepG2 human hepatoma cells and human organ samples (lung, liver, kidney, and small intestine) and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [35S]sulfate in the presence of each of the eight opioid drugs, showed the generation and release of corresponding [35S]sulfated derivatives. Five of the eight opioid drugs, hydromorphone, oxymorphone, butorphanol, nalorphine, and naltrexone, appeared to be more strongly sulfated in HepG2 cells than were the other three, morphine, nalbuphine, and levorphanol. Differential sulfating activities toward the opioid drugs were detected in cytosol or S9 fractions of human lung, liver, small intestine, and kidney, with the highest activities being found for the liver sample. A systematic analysis using eleven known human SULTs and kinetic experiment revealed SULT1A1 as the major responsible SULTs for the sulfation of oxymorphone, nalbuphine, nalorphine, and naltrexone, SULT1A3 for the sulfation of morphine and hydromorphone, and SULT2A1 for the sulfation of butorphanol and levorphanol. Collectively, the results obtained imply that sulfation may play a significant role in the metabolism of the tested opioid drugs in vivo.
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DOI：
10.1016/j.jsbmb.2004.01.005
发表时间：
2004-04-01
影响因子：
4.1
作者：
Falany, JL;Macrina, N;Falany, CN
通讯作者：
Falany, CN
影响因子：
5.8
作者：
Froelich, Nadine;Dees, Christian;Zenk, Meinhart H.
通讯作者：
Zenk, Meinhart H.
影响因子：
3.8
作者：
BROWN, CE;ROERIG, SC;FUJIMOTO, JM
通讯作者：
FUJIMOTO, JM
影响因子：
2.9
作者：
BRADFORD, MM
通讯作者：
BRADFORD, MM
影响因子：
3.9
作者：
Bostrom, Emma;Simonsson, Ulrika S. H.;Hammarlund-Udenaes, Margareta
通讯作者：
Hammarlund-Udenaes, Margareta