Embryonic growth inhibition induced by cocaine is associated with the suppression of ornithine decarboxylase activity.
Cocaine use during pregnancy results in significant increases in fetal morbidity and mortality. Multiple maternal and environmental variables influence the fetal response to cocaine, and growth suppression of the developing child is frequently associated with in utero cocaine exposure. Using intact chick embryos as well as cultured embryonic tissue as a model, we report that the growth suppression induced by cocaine exposure is correlated with molecular changes occurring directly in the embryonic cells and that these molecular changes appear to be distinct from other maternal, placental, or environmental effects of the drug, including anoxia. Specifically, embryonic cocaine exposure suppresses the normal developmental increase in ornithine decarboxylase (ODC) enzymatic activity. The loss of ODC activity during the early stages of development is dose dependent and is correlated with the degree of growth suppression. The cocaine-induced loss of decarboxylase activity is specific to ODC, but cocaine, per se, has no effect on ODC activity in vitro. Moreover, a single dose of exogenous putrescine given at 120 hr of incubation blocks the cocaine-induced growth suppression. In cultured embryonic tissue, cocaine exposure inhibits the ability of a known trophic factor (insulin) to induce growth and also blocks the associated increase in ODC activity. Preliminary data suggest that cocaine hinders the binding of insulin to embryonic cells. Because ODC is a focal enzyme for the regulation of growth, the data suggest that cocaine-induced changes in the mitogenic induction of embryonic/fetal ODC activity may be a part of the biochemical mechanism by which cocaine-induced growth inhibition occurs.
Sandstrom
L P
LP
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, North Carolina 27834.
Pennington
S N
SN
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D007328:Insulin; D065108:Ornithine Decarboxylase Inhibitors; D009955:Ornithine Decarboxylase; D003042:Cocaine; D011700:Putrescine; D013936:Thymidine; D000518:Eflornithine