CHARACTERIZATION OF CA2-ASPARAGINE IN RAT HEPATOMA-CELLS USING CA2+ FLOW INHIBITORS( FLOWS ESSENTIAL IN ORNITHINE DECARBOXYLASE INDUCTION BY L)

L-Asparagine stimulates bi-directional Ca2+ flows and induces ornithin e decarboxylase in Reuber H-35 hepatoma cells. Previously it has been shown that these effects are completely, but reversibly inhibited by l anthanum chloride. In this study we examined the role(s) of Ca2+ flows using more specific Ca2+ flow inhibitors. It was shown that ornithine decarboxylase induction was inhibited by CdCl2 and verapamil at conce ntrations above 1 mu M and 100 mu M respectively, but was unaffected b y as much as 300 mu M NiCl2, 1 mM nifedipine, or 10 mu M omega-conotox in. Enzyme induction was blocked by the Ca2+-ATPase pump antagonists v anadate and Compound 48/80 in a dose-dependent manner. These results, taken together with the observations that extracellular Ca2+ is essent ial for enzyme induction but a substantial elevation of cytoplasmic [C a2+] is not, suggest that Ca2+ inflow independent of the receptor-acti vated Ca2+ channels, and the Ca2+-ATPase mediated Ca2+ out-flow, are b oth important factors in the action of L-asparagine.