Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin.
Liver parenchymal cells were isolated from adult rats and cultured in collagen-coated plastic petri dishes in serum-free medium. Glucagon induced 4- to 5-fold increases in alpha-aminoisobutyric acid (AIB) transport within 6 hr. Dexaemthasone had no direct effect on AIB transport but greatly potentiated the induction by glucagon ("permissive effect"). Levels of 3':5'-cyclic AMP increased 30- to 100-fold within 30 min after glucagon addition to cultures that had been treated with dexamethasone, and dibutyryl cyclic AMP mimicked the glucagon induction of AIB transport. Additionally, dexamethasone exerted a "permissive" effect on induction of AIB transport by dibutyryl cyclic AMP, whereas the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine induced AIB transport only in cultures that had been treated with dexamethasone. Induction of AIB transport was not dependent upon the continued presence of glucagon, but induced AIB transport activity decayed to uninduced levels within 3-4 hr after glucagon removal. The protein syntesis inhibitors puromycin and cycloheximide inhibited both induction and decay of glucagon induced AIB transport, but had a stabilizing effect if added once induction or decay had commenced. Unlike cycloheximide, the inhibitory effect of puromycin on the glucagon induction of AIB transport was reversible.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003513:Cycloheximide / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011691:Puromycin / Q000494:pharmacology*; D051381:Rats; D014970:Xanthines / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D014970:Xanthines; D011691:Puromycin; D003994:Bucladesine; D003907:Dexamethasone; D005934:Glucagon; D003513:Cycloheximide; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases