A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 2. Mechanism of action.
1. An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2. The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3. It was found that the amplifier increased both incorporation of [3H]dexamethasone into the cytosol and binding of [3H]dexamethasone of cytosol protein and that it decreased decay of the [3H]dexamethasone-protein complex.
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D011513:Proteus mirabilis / Q000032:analysis; D051381:Rats; D013997:Time Factors; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D003609:Dactinomycin; D003907:Dexamethasone; D014444:Tyrosine Transaminase