Prostaglandin E2 does not regulate total or myofibrillar protein breakdown in incubated skeletal muscle from normal or septic rats.
The role of prostaglandins in the regulation of muscle protein breakdown is controversial. We examined the influence of arachidonic acid (5 microM), prostaglandin E2 (PGE2) (2.8 microM) and the prostaglandin-synthesis inhibitor indomethacin (3 microM) on total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscles incubated under different conditions in vitro. In other experiments, the effects of indomethacin, administered in vivo to septic rats (3 mg/kg, injected subcutaneously twice after induction of sepsis by caecal ligation and puncture) on plasma levels and muscle release of PGE2 and on total and myofibrillar protein breakdown rates were determined. Total and myofibrillar proteolysis was assessed by measuring production by incubated muscles of tyrosine and 3-methylhistidine respectively. Arachidonic acid or PGE2 added during incubation of muscles from normal rats did not affect total or myofibrillar protein degradation under a variety of different conditions in vitro. Indomethacin inhibited muscle PGE2 production by incubated muscles from septic rats, but did not lower proteolytic rates. Administration in vivo of indomethacin did not affect total or myofibrillar muscle protein breakdown, despite effective plasma levels of indomethacin with decreased plasma PGE2 levels and inhibition of muscle PGE2 release. The present results suggest that protein breakdown in skeletal muscle of normal or septic rats is not regulated by PGE2 or other prostaglandins.
Hasselgren
P O
PO
Department of Surgery, University of Cincinnati, OH 45267-0558.
Zamir
O
O
James
J H
JH
Fischer
J E
JE
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000503:physiopathology*; D014443:Tyrosine / Q000378:metabolism
D001095:Arachidonic Acids; D008762:Methylhistidines; D009124:Muscle Proteins; D016718:Arachidonic Acid; D014443:Tyrosine; D003513:Cycloheximide; D015232:Dinoprostone; C028118:3-methylhistidine; D007213:Indomethacin