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. Pregnant rats received 62 mg/kg of cocaine hydrochloride by intraperitoneal (IP) injection as a divided daily dose on gestation days 8-19 inclusive. Fetal body weights were significantly decreased by 19% in the cocaine group, while placental weights were unchanged. Placental apical membrane vesicles were prepared from control and cocaine-treated animals, and marker enzyme enrichments for alkaline phosphatase and [3H]-dihydroalprenolol binding did not differ between cocaine and control groups. Rates of uptake (10 sec) of selected radiolabeled amino acids were measured utilizing a rapid filtration technique. Na(+)-dependent apical membrane [3H]-glutamine transport (50 microM) was reduced by 95% (p < 0.05) in cocaine-treated compared to control placentas. Uptake of 50 microM [3H]-methyl aminoisobutyric acid (MeAIB) into apical membranes was also decreased by 43% (p < 0.05) in cocaine membranes. Na(+)-independent [3H]-arginine transport (10 microM), however, did not differ between control or cocaine-treated groups. In summary, chronic cocaine administration selectively inhibited the transport of glutamine and MeAIB into apical membrane vesicles, but had minimal effect on arginine transport. We postulate that this diminution in uptake may contribute to the fetal growth retardation noted in our model.
Novak
D A
DA
Department of Pediatrics, University of Florida, Gainesville 32610, USA.
Beveridge
M J
MJ
Salhab
A S
AS
Tebbett
I R
IR
Shiverick
K T
KT
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000621:Aminoisobutyric Acids; D005973:Glutamine; C017911:2-(methylamino)isobutyric acid; D001120:Arginine; D003042:Cocaine