Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Dimethylethanolamine (0.5-1 mM), added to serum-starved NIH 3T3 fibroblasts, stimulated DNA synthesis 11-32-fold, and it also greatly enhanced the relatively modest (15-20-fold) mitogenic effect of insulin. Ethanolamine and monomethylethanolamine alone had no effects on DNA synthesis, but they also enhanced the stimulatory effect of insulin, although less effectively than dimethylethanolamine did. Lower concentrations (2.5-5 microg/ml) of compound D 609 (tricyclo-9-yl-xanthogenate), which had no effects on phospholipase activities, synergistically enhanced the combined effects of ethanolamine analogs and insulin on DNA synthesis without affecting the synthesis of ethanolamine phospholipids. These results suggest that ethanolamine and its analogues, formed by phospholipase D-mediated hydrolysis of ethanolamine phospholipids, may have growth regulatory functions independent of their role as phospholipid precursors.