Amino acid-dependent inactivation of glucagon-induced System A transport activity in cultured rat hepatocytes.
Hepatocytes isolated from glucagon-treated rats contain stimulated System A activity. If these cells are placed in primary culture, the enhanced transport decays rapidly provided the culture medium contains substrate amino acids. This amino acid-dependent inactivation can be composed of trans-inhibition (protein synthesis-independent), repression (protein synthesis-dependent), or both depending on the particular substrate tested. Repression was most prominently observed with a group of small neutral amino acids that are commonly found in proteins. A strong trans-inhibition response was induced by a variety of amino acid analogs. Amino acids showing no reactivity with System A produced neither trans-inhibition nor repression. Repression of System A activity in culture was blocked by inhibitors of both RNA and protein synthesis. In contrast to inhibitors of RNA biosynthesis such as actinomycin and alpha-amanitin, inhibitors of poly(A) polymerase (cordycepin and adenine-9-beta-D-arabinopyranoside) did not prevent the inactivation of the transport activity. These results demonstrate that both the stimulation of activity and the turnover of the hepatic System A activity are controlled at the transcriptional level.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005934:Glucagon / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D005934:Glucagon