Regulation of protein synthesis in isolated hepatocytes by calcium-mobilizing hormones.
The incorporation of leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of normal liver cells isolated from fed, adult male rats. Ca2+-restored cells incorporated amino acid 5-10-fold more rapidly than did Ca2+-depleted cells for incubation periods up to 1 hr. Readdition of Ca2+ at supraphysiologic concentrations (3 mM) to depleted cells restored the rate of incorporation within 8-10 min, whereas lesser concentrations of the cation acted more slowly. Vasopressin and alpha-adrenergic agonists rapidly (in minutes) inhibited amino acid incorporation to variable degrees in liver cells, with pronounced inhibitions (40-75%) occurring at moderate (0.1-1 mM) extracellular Ca2+ concentrations and smaller inhibitions (10-30%) occurring at supraphysiologic concentrations of the cation. Hormonally produced inhibitions were more intense at acid pH than at alkaline pH. The effects of epinephrine were mediated through alpha 1-adrenergic receptors and were not additive with those of vasopressin at saturating concentrations. It is proposed that these hormones, which are known to mobilize sequestered Ca2+ within liver cells, inhibit amino acid incorporation by influencing a Ca2+ requirement associated with protein synthesis.
Brostrom
C O
CO
Bocckino
S B
SB
Brostrom
M A
MA
Galuska
E M
EM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014667:Vasopressins / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000596:Amino Acids; D006728:Hormones; D014316:Tritium; D014667:Vasopressins; D004533:Egtazic Acid; D007930:Leucine; D008274:Magnesium; D002118:Calcium; D004837:Epinephrine