EFFECT OF CHRONIC COCAINE ADMINISTRATION ON AMINO-ACID-UPTAKE IN RAT PLACENTAL MEMBRANE-VESICLES

This study evaluated the effects of chronic exposure to cocaine during pregnancy on amino acid uptake in placental membrane vesicles. Pregna nt rats received 62 mg/kg of cocaine hydrochloride by intraperitoneal (IF) injection as a divided daily dose on gestation days 8-19 inclusiv e. Fetal body weights were significantly decreased by 19% in the cocai ne group, while placental weights were unchanged. Placental apical mem brane vesicles were prepared from control and cocaine-treated animals, and marker enzyme enrichments for alkaline phosphatase and [H-3]-dihy droalprenolol binding did not differ between cocaine and control group s. Rates of uptake (10 sec) of selected radiolabeled amino acids were measured utilizing a rapid filtration technique. Na+-dependent apical membrane [H-3]-glutamine transport (50 mu M) was reduced by 95% (p < 0 .05) in cocaine-treated compared to control placentas. Uptake of 50 mu M [H-3]-methyl aminoisobutyric acid (MeAIB) into apical membranes was also decreased by 43% (p < 0.05) in cocaine membranes. Na+-independen t [H-3]-arginine transport (10 mu M), however, did not differ between control or cocaine-treated groups. In summary, chronic cocaine adminis tration selectively inhibited the transport of glutamine and MeAIB int o apical membrane vesicles, but had minimal effect on arginine transpo rt. We postulate that this diminution in uptake may contribute to the fetal growth retardation noted in our model.