Anesthesia with Halothane and Nitrous Oxide Alters Protein and Amino Acid Metabolism in Dogs

Horber, Fritz F.; Krayer, S.; Rehder, Kai; Haymond, Morey W.

doi:10.1097/00000542-198809000-00006

Cited by 37 publications

(19 citation statements)

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“…This has been reported in a number of different systems, including intact animals (23)(24)(25), perfused organs (10,40,41), tissue slices in culture (15)(16)(17)(18), and cells in culture (3,6,8,21,35). Studies regarding effects of volatile anesthetics on protein synthesis in perfused rat liver, the system employed in the work reported here, demonstrate that halothane exposure produces a rapid and dose-dependent inhibition of translation initiation affecting synthesis of both secreted and retained proteins (10,12).…”

mentioning

confidence: 55%

Inhibition of mammalian translation initiation by volatile anesthetics

Palmer¹,

Rannels²,

Kimball³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Volatile anesthetics are essential for modern medical practice, but sites and mechanisms of action for any of their numerous cellular effects remain largely unknown. Previous studies with yeast showed that volatile anesthetics induce nutrient-dependent inhibition of growth through mechanisms involving inhibition of mRNA translation. Studies herein show that the volatile anesthetic halothane inhibits protein synthesis in perfused rat liver at doses ranging from 2 to 6%. A marked disaggregation of polysomes occurs, indicating that inhibition of translation initiation plays a key role. Dose-and time-dependent alterations that decrease the function of a variety of translation initiation processes are observed. At 6% halothane, a rapid and persistent increase in phosphorylation of the ␣-subunit of eukaryotic translation initiation factor (eIF)2 occurs. This is accompanied by inhibition of activity of the guanine nucleotide exchange factor eIF2B that is responsible for GDP-GTP exchange on eIF2. At lower doses, neither eIF2␣ phosphorylation nor eIF2B activity is altered. After extended exposure to 6% halothane, alterations in two separate responses regulated by the target of rapamycin pathway occur: 1) redistribution of eIF4E from its translation-stimulatory association with eIF4G to its translation-inactive complex with eIF4E-binding protein-1; and 2) decreased phosphorylation of ribosomal protein S6 (rpS6) with a corresponding decrease in active forms of a kinase that phosphorylates rpS6 (p70 S6K1 ). Changes in the association of eIF4E and eIF4G are observed only after extended exposure to low anesthetic doses. Thus dose-and time-dependent alterations in multiple processes permit liver cells to adapt translation to variable degrees and duration of stress imposed by anesthetic exposure. halothane; eukaryotic translation initiation factor 2␣ phosphorylation; mammalian target of rapamycin pathway ALTHOUGH VOLATILE ANESTHETICS revolutionized medical practice when introduced in 1846, the mechanisms of action responsible for the physiological effects of these drugs remain essentially unknown. In addition to affecting cells of the central nervous system, these drugs affect all cells, tissues, and organisms examined (4,26,36). Molecular genetic studies with the small, relatively simple eukaryote Saccharomyces cerevisiae (yeast) provide an opportunity for gaining insight regarding physiologically relevant effects of these drugs (28) and generating hypotheses that are testable in more complex eukaryotes. Extensive similarities exist between the activity of these drugs in mammals and simpler eukaryotes, such as yeast, suggesting conservation of cellular mechanisms responsible for the responses (28,34,45). These similarities include rapid and reversible induction of responses, a sharp dose-response curve, correlation between the lipophilicity of various anesthetics and their potency for inducing responses (termed the Meyer-Overton relationship), additivity of doses of different anesthetics in producing effects, and lack of effec...

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mentioning

confidence: 55%

Inhibition of mammalian translation initiation by volatile anesthetics

Palmer¹,

Rannels²,

Kimball³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…Nonoxidative leucine disappearance (NOLD), an indicator of whole body protein synthesis, was only increased in subjects treated with rhGH alone. The ratio of leucine oxidation to NOLD, an indicator of whole body leucine catabolism (39), was increased during prednisone treatment alone, decreased with rhGH therapy alone, but unchanged in subjects receiving both rhGH and prednisone when compared to placebo-treated subjects. The systemic availability of enterally infused [3H]leucine and ['3C]leucine was 87% or greater in all groups, although slightly (but not significantly) higher in both groups treated with prednisone (Table III).…”

Section: Resultsmentioning

confidence: 92%

Human growth hormone prevents the protein catabolic side effects of prednisone in humans.

Horber¹,

Haymond²

1990

J. Clin. Invest.

397

169

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Prednisone treatment causes protein wasting and adds additional risks to a patient, whereas human growth hormone (hGH) treatment causes positive nitrogen balance. To determine whether concomitant administration of hGH prevents the protein catabolic effects of prednisone, four groups of eight healthy volunteers each were studied using isotope dilution and nitrogen balance techniques after 7 d of placebo, hGH alone (0

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“…In contrast to propofol, high doses of opioids, 1 and neuraxial techniques, inhalational agents have been shown to accentuate the hyperglycemic response to surgery. 5,6 The administration of corticosteroids for the prevention of postoperative nausea and vomiting, even in small doses, further exacerbates hyperglycemia in non-diabetic patients. 7,8 Unexpectedly large numbers of patients show abnormal glucose homeostasis before surgery.…”

Section: Glucose Metabolismmentioning

confidence: 99%