Singer S S, Ansel A Z, Van Brunt N, Torres J, Galaska E G
Biochem Pharmacol. 1984 Nov 1;33(21):3485-90. doi: 10.1016/0006-2952(84)90124-2.
The effects of ten drugs on hepatic glucocorticoid sulfotransferase activity (HGSTA) were examined in male rats. The enzyme activity per 100 g body weight was elevated 152, 94.9, 140, 140, 73.1, 63.9, 76.9, and 140% after administration of daily i.p. doses of 111 mg spironolactone/kg (6-10 days), 66.7 mg WIN-24540/kg (6-10 days), 150 mg metyrapone/kg (19-31 days), 33.3 mg pentachlorophenol/kg (9-16 days), 16.5 mg aspirin/kg (10-16 days), 90.5 mg alloxan/kg (23.27 days), 104 mg aminoglutethimide/kg (12-20 days), and 16.8 mg propranolol/kg (21-27 days). Shorter experimental periods or lower drug doses caused smaller effects on HGSTA. Most notably, spironolactone (111 mg/kg) and WIN-24540 (66.7 mg/kg) caused 50-75% elevation of HGSTA in 2 days. Effects of WIN-24540, aspirin and pentachlorophenol were due mostly to elevation of hepatic levels of sulfotransferase III (STIII), the glucocorticoid-preferring sulfotransferase of rat liver. Effects of the other test drugs were due to elevation of hepatic levels of sulfotransferases I and II (STI and STII), which much prefer dehydroepiandrosterone as substrate, but also catalyze glucocorticoid sulfation. Enzyme inhibition studies showed that the test drugs interacted with the HGSTA in vitro in a fashion that appeared to be related to the in vivo effects already described. None of the drugs interacted exclusively with STI, STII or STIII in vitro. However, some differences of the strengths of individual drug-sulfotransferase interactions were observed. The drug effects are discussed in relation to drug and glucocorticoid actions.
在雄性大鼠中检测了十种药物对肝脏糖皮质激素磺基转移酶活性（HGSTA）的影响。每日腹腔注射剂量为111 mg螺内酯/ kg（6 - 10天）、66.7 mg WIN - 24540 / kg（6 - 10天）、150 mg美替拉酮/ kg（19 - 31天）、33.3 mg五氯苯酚/ kg（9 - 16天）、16.5 mg阿司匹林/ kg（10 - 16天）、90.5 mg四氧嘧啶/ kg（23 - 27天）、104 mg氨鲁米特/ kg（12 - 20天）和16.8 mg普萘洛尔/ kg（21 - 27天）后，每100 g体重的酶活性分别升高了152%、94.9%、140%、140%、73.1%、63.9%、76.9%和140%。较短的实验周期或较低的药物剂量对HGSTA的影响较小。最显著的是，螺内酯（111 mg / kg）和WIN - 24540（66.7 mg / kg）在2天内使HGSTA升高了50 - 75%。WIN - 24540、阿司匹林和五氯苯酚的作用主要是由于肝脏中磺基转移酶III（STIII）水平的升高，STIII是大鼠肝脏中更倾向于糖皮质激素的磺基转移酶。其他受试药物的作用是由于肝脏中磺基转移酶I和II（STI和STII）水平的升高，它们更倾向于以脱氢表雄酮为底物，但也催化糖皮质激素的硫酸化。酶抑制研究表明，受试药物在体外与HGSTA的相互作用方式似乎与上述体内效应有关。在体外，没有一种药物仅与STI、STII或STIII相互作用。然而，观察到了个别药物 - 磺基转移酶相互作用强度的一些差异。结合药物和糖皮质激素的作用对药物效应进行了讨论。
