Growth hormone attenuates Na(+)-dependent hepatic amino acid transport in endotoxemic rats.
The effects of human growth hormone (GH) on hepatic Na(+)-dependent amino acid transport were studied in endotoxin-treated rats. Adult rats received GH (6 mg/kg BW subQ q 12 hours x 4 doses) or vehicle prior to a single dose of Escherichia coli endotoxin (LPS, 7.5 mg/kg BW IP). Four hours after LPS administration, livers were excised and hepatocyte plasma membrane vesicles (HPMVs) were prepared by differential and Percoll density gradient centrifugation. Hepatocyte plasma membrane vesicle transport of [3H]-MeAIB, a highly selective system A substrate, [3H]-glutamine, a selective system N substrate, and [35S]-cysteine, a system ASC substrate, were measured by a rapid mixing/filtration technique. Vesicle purity and functionality were assessed by marker enzyme measurements and classic overshoots and timecourses that showed similar vesicle size. Endotoxin treatment resulted in a two-fold increase in the activities of systems N and ASC, which was the result of an increase in carrier Vmax (Km was unchanged), and a four-fold stimulation of system A. Pre-treatment with GH diminished the endotoxin-induced increase in Na(+)-dependent amino acid transport by 60%-80%; this reduction in carrier-mediated transport activity was a result of a decrease in Vmax, consistent with a decrease in the number of functional transporter proteins in the plasma membrane. Growth hormone treatment attenuates the endotoxin-induced increase in the activities of the major Na(+)-dependent transporters in rat liver. This may diminish hepatic ureagenesis and spare amino acids for peripheral protein synthesis and thereby explain, at least in part, the ability of growth hormone to promote positive nitrogen balance in catabolic states.
Inoue
Y
Y
Department of Surgery, University of Florida College of Medicine, Gainesville.
Fallon
W
W
Souba
W W
WW
D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005973:Glutamine / Q000378:metabolism; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D006728:Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014115:Toxemia / Q000378:metabolism*
D000596:Amino Acids; D004731:Endotoxins; D006728:Hormones; D011994:Recombinant Proteins; D005973:Glutamine; D019382:Human Growth Hormone; D013006:Growth Hormone