The spontaneous induction of glutamine synthetase in pig hepatocytes cocultured with RL-ET-14 cells is completely inhibited by trijodothyronine and okadaic acid

Cocultivation of primary pig hepatocytes with RL-ET-14 cells, an endothelial-like cell line resulted in spontaneous induction of glutamine synthetase (GS)activity in the hepatocytes by more than 10-fold within 120 h to 144 h. Hepatocyte-specific induction was confirmed by immunocytochemistry. Addition of trijodothyronine (T-3) to the culture medium inhibited the induction in a concentration dependent manner. No comparable influence of T-3 was Seen with pure cultures of either cell type suggesting that only the spontaneous induction was affected. Other hormones such as glucagon, insulin, growth hormone, epinephrine and testosterone did not interfere with the induction. Addition of several protein kinase-inhibitors such as staurosporine and genistein were without influence. However, a strong inhibition was found after addition of okadaic acid in nanomolar concentrations indicating an involvement of protein-phosphatase 2A in the induction process. (C) 1998 Academic Press.