title: Attenuation of the endotoxin-stimulated increase in hepatic amino acid transport with a glucocorticoid receptor antagonist.
abstract: 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.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: B P
authors.initials: BP
authors.lastname: Bode
authors.forename: S
authors.initials: S
authors.lastname: Abcouwer
authors.forename: W W
authors.initials: WW
authors.lastname: Souba
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005938:Glucocorticoids / Q000502:physiology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: D000596:Amino Acids; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D015735:Mifepristone