Anundi I, Kauffman F C, el-Mouelhi M, Thurman R G
Arch Toxicol. 1987;60(1-3):69-72. doi: 10.1007/BF00296950.
4-Methylumbelliferyl sulfate was used to characterize sulfatase activity in periportal and pericentral regions of the liver lobule in the perfused rat liver. Following infusion of 1.5 mM of this organic sulfatester, free 4-methylumbelliferone and 4-methylumbelliferyl glucuronide were formed at rates of 13 and 9 mumoles/g/h, respectively, in livers from fasted, phenobarbital-treated rats. 5-Pregnen-3 beta-ol, 20-one sulfate inhibited hydrolysis and metabolite production completely, whereas perfusion with nitrogen-saturated perfusate or FCCP decreased total metabolite formation by only 30%. 4-Methylumbelliferone formed from the hydrolysis of 4-methylumbelliferyl sulfate was monitored with micro-light guides placed on periportal and pericentral areas of the liver lobule. Detection of the desulfated product was always greater in the downstream region, i.e., infusion of 4-methylumbelliferyl sulfate produced a higher fluorescence signal in pericentral areas when perfusion was in the anterograde direction, while periportal areas demonstrated higher activity during perfusion in the retrograde direction. Perfusion with nitrogen-saturated perfusate abolished these differences. Taken together, these data suggest that uptake of organic sulfateesters is partially energy dependent, follows the hepatic oxygen gradient inversely, and is a major rate determinant for sulfatase activity in the liver.
4-甲基伞形酮基硫酸酯被用于表征灌注大鼠肝脏肝小叶门周和中央周围区域的硫酸酯酶活性。在灌注1.5 mM这种有机硫酸酯后，禁食且经苯巴比妥处理的大鼠肝脏中，游离4-甲基伞形酮和4-甲基伞形酮基葡糖醛酸分别以13和9微摩尔/克/小时的速率形成。5-孕烯-3β-醇-20-酮硫酸酯完全抑制水解和代谢产物生成，而用氮气饱和的灌注液或FCCP灌注仅使总代谢产物生成减少30%。通过放置在肝小叶门周和中央周围区域的微型光导监测由4-甲基伞形酮基硫酸酯水解形成的4-甲基伞形酮。在下游区域，脱硫产物的检测量总是更高，即当灌注为顺行方向时，灌注4-甲基伞形酮基硫酸酯在中央周围区域产生更高的荧光信号，而在逆行灌注期间门周区域表现出更高的活性。用氮气饱和的灌注液灌注消除了这些差异。综上所述，这些数据表明有机硫酸酯的摄取部分依赖能量，与肝脏氧梯度呈反向关系，并且是肝脏中硫酸酯酶活性的主要速率决定因素。
