Induction of Ornithine Decarboxylase in Guinea Pig Lymphocytes by the Divalent Cation Ionophore A 23187 and Phytohemagglutinin

Abstract

Ornithine decarboxylase activity increased rapidly in guinea pig lymphocytes and reached a peak 5h after the addition of A 23187 to the cell culture. The optimum dose of A 23187 for the induction of ornithine decarboxylase was similar to that for the stimulation of DNA synthesis. Induction of ornithine decarboxylase by A 23187 or phytohemagglutinin was inhibited by the addition of ethylene glycol bis(β-aminoethylether)-N, N'-tetraacetic acid to the cell cultures and the inhibition was overcome by the addition of CaCl₂, but not MgCl₂. The effects of phytohemagglutinin on Ca²⁺ influx and efflux were less than those of A 23187. In contrast, phytohemagglutinin was more potent than A 23187 in stimulating ornithine decarboxylase activity. These results suggest that Ca²⁺ is necessary to induce ornithine decarboxylase, but the extent of increase of cytosolic Ca²⁺ concentration does not necessarily coincide with that of ornithine decarboxylase activity.
Treatment with low concentrations of cytochalasin B inhibited A 23187-induced ornithine decarboxylase activity, but not phytohemagglutinin-induced activity. The addition of dibutyryl cAMP or cholera toxin to cell cultures inhibited phytohemagglutinin-induced ornithine decarboxylase activity, while it rather enhanced A 23187-induced activity. Phytohemagglutinin and A 23187 in combination failed to induce ornithine decarboxylase activity more effectively than phytohemagglutinin alone, but in combination with lipopolysaccharide, A 23187 had an additive effect. These results suggest that there are substantial differences between A 23187 and phytohemagglutinin as regards the mechanism of induction of ornithine decarboxylase, although both mitogens act on the same lymphocyte population.