Regulation of ornithine decarboxylase activity by cyclic AMP in guinea pig lymphocytes: transcriptional and post-transcriptional control

Abstract

Induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in phytohemagglutinin-stimulated lymphocytes was suppressed by the administration of dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine. This inhibition of ornithine decarboxylase induction was overcome by removing the chemicals from the lymphocyte culture. However, the recovery of ornithine decarboxylase induction by washout of the chemicals did not occur when actinomycin D, cordycepin or alpha-amanitin was added to the cultures, suggesting that the synthesis of mRNA directed to ornithine decarboxylase was reduced in dibutyryl cyclic AMP- and 3-isobutyl-1-methylxanthine-treated cells. Moreover, the decay of ornithine decarboxylase activity in the cells treated with phytohemagglutinin plus dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine was significantly slower than that of control cells stimulated with phytohemagglutinin alone. The difference of the decrease in ornithine decarboxylase activity between dibutyryl cyclic AMP- and 3-isobutyl-1-methylxanthine-treated and control cells was observed when actinomycin D was added to the culture, but not when cycloheximide was added. Therefore, prevention of ornithine decarboxylase decay by cyclic AMP may be post-transcriptional events, but not post-translational events.