Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body.
The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis (K(s)) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although K(s) remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels approximately 6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body.
Yamaoka
Ippei
I
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Naruto, Tokushima 772-8601, Japan. yamaokih@otsukakj.co.jp
Doi
Masako
M
Nakayama
Mitsuo
M
Ozeki
Akane
A
Mochizuki
Shinji
S
Sugahara
Kunio
K
Yoshizawa
Fumiaki
F
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D022722:Thermogenesis / Q000187:drug effects*
D000596:Amino Acids; D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; C546845:mTOR protein, rat; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D015742:Propofol