Evidence that inhibition of muscle amino acid uptake during endotoxemia is not mediated by glucocorticoids.
Sepsis and endotoxemia are associated with increased muscle protein breakdown and inhibited amino acid uptake. Glucocorticoids are important for the regulation of muscle protein breakdown in catabolic conditions; in contrast, the role of glucocorticoids in the regulation of muscle amino acid transport during sepsis or endotoxemia is not known. The present study was designed to test the role of glucocorticoids in the regulation of muscle amino acid uptake during endotoxemia. Amino acid transport, determined as uptake of 3H-alpha-aminoisobutyric acid (AIB) by incubated soleus muscles in vitro, was reduced by approximately 40% 2 hours after intraperitoneal (IP) injection of 10 micrograms/kg endotoxin in rats. Administration of 5 mg/kg of the glucocorticoid receptor antagonist RU 38486 2 hours before endotoxin injection did not affect the inhibition of amino acid uptake. In vitro addition of plasma from endotoxemic rats to incubated rat soleus muscles inhibited amino acid uptake by approximately 30%. This effect of endotoxic plasma also was noted when muscles were from rats that had been treated with RU 38486 and when RU 38486 was present in the incubation medium. Results confirm previous reports of reduced muscle amino acid transport during endotoxemia and of the presence of a circulating factor that inhibits muscle amino acid uptake in this condition. Data suggest that inhibited muscle amino acid transport during endotoxemia is not regulated by glucocorticoids.
Zamir
O
O
Department of Surgery, University of Cincinnati Medical Center, OH 45267-0558.
James
J H
JH
Hasselgren
P O
PO
Fischer
J E
JE
D000621:Aminoisobutyric Acids / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000621:Aminoisobutyric Acids; D004731:Endotoxins; D005938:Glucocorticoids; C100049:2-aminoisobutyric acid; D015735:Mifepristone; D003345:Corticosterone