Nicolas Laurent B, Fry Jonathan P
Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK.
Brain Res. 2007 Oct 12;1174:92-6. doi: 10.1016/j.brainres.2007.07.078. Epub 2007 Aug 19.
Intraperitoneal injection of adult male mice with the neuroactive steroid dehydroepiandrosterone sulfate (DHEAS) at 1 and 40 mg/kg caused dose-dependent increases in the concentration of both this compound and its corresponding free steroid DHEA in brain within 1 h of injection. Pretreatment of these animals for 24 h with the steroid sulfatase inhibitor COUMATE at a dose (10 mg/kg, p.o.) shown previously to cause almost complete inhibition of this enzyme in liver and brain was expected to increase the amount of the DHEAS dose reaching the brain. Surprisingly however, the increases in brain concentrations of DHEAS and DHEA after injection of DHEAS i.p. were attenuated by pretreatment with COUMATE. The results suggest that the arylsulfamate based steroid sulfatase inhibitors such as COUMATE interfere with the influx of the DHEAS anion into the brain.
给成年雄性小鼠腹腔注射1毫克/千克和40毫克/千克的神经活性甾体硫酸脱氢表雄酮（DHEAS），在注射后1小时内，脑内该化合物及其相应的游离甾体脱氢表雄酮（DHEA）的浓度呈剂量依赖性增加。先前已证明，以10毫克/千克（口服）的剂量用甾体硫酸酯酶抑制剂香豆酸对这些动物进行24小时预处理，可使肝脏和脑中的该酶几乎完全受到抑制，预计这会增加到达脑内的DHEAS剂量。然而，令人惊讶的是，香豆酸预处理减弱了腹腔注射DHEAS后脑内DHEAS和DHEA浓度的增加。结果表明，基于芳基氨基磺酸酯的甾体硫酸酯酶抑制剂（如香豆酸）会干扰DHEAS阴离子流入脑内。
