Inoue Y, Bode B P, Abcouwer S, Souba W W
Department of Surgery, Massachusetts General Hospital, Boston 02114, USA.
J Surg Res. 1995 Jun;58(6):693-701. doi: 10.1006/jsre.1995.1109.
The role of the glucocorticoid hormones in mediating the accelerated hepatic amino acid transport that is characteristic of endotoxemia was investigated. To determine the role of these steroid hormones, rats that received endotoxin (LPS) were pretreated with the glucocorticoid receptor antagonist RU38486. The activities of the Na(+)-dependent amino acid transport systems A, ASC, and N and the Na(+)-independent systems L, y+, n, b0,+, and asc in hepatic plasma membrane vesicles were measured 4 hr after exposure to LPS. Endotoxin treatment resulted in time- and dose-dependent 5-fold (System A), 2.5-fold (System N), 2.6-fold (System ASC), and 2-fold (System y+ and b0,+) increases in transport activity attributable to an increase in carrier Vmax. The activities of L, asc, and n were unchanged by LPS administration. Pretreatment of endotoxemic animals with RU38486 attenuated the LPS-induced enhancement in transport activity by 20-60% by diminishing carrier Vmax, with no effect on transport Km. We conclude that the marked increase in hepatic amino acid transport activity that occurs during endotoxemia requires participation of the glucocorticoid hormones.
研究了糖皮质激素在内毒素血症所特有的加速肝脏氨基酸转运过程中的作用。为了确定这些类固醇激素的作用，给接受内毒素（LPS）的大鼠预先使用糖皮质激素受体拮抗剂RU38486。在暴露于LPS 4小时后，测量肝细胞膜囊泡中依赖Na⁺的氨基酸转运系统A、ASC和N以及不依赖Na⁺的系统L、y⁺、n、b0,+和asc的活性。内毒素处理导致转运活性出现时间和剂量依赖性增加，系统A增加5倍、系统N增加2.5倍、系统ASC增加2.6倍、系统y⁺和b0,+增加2倍，这归因于载体Vmax的增加。给予LPS后，L、asc和n的活性未发生变化。用RU38486对内毒素血症动物进行预处理，通过降低载体Vmax使LPS诱导的转运活性增强减弱20 - 60%，而对转运Km无影响。我们得出结论，内毒素血症期间肝脏氨基酸转运活性的显著增加需要糖皮质激素的参与。
