The effects of cocaine on neutral amino acid uptake by human placental basal membrane vesicles.
OBJECTIVE
Prior studies have demonstrated that cocaine binds to human placental microvillous membrane vesicles at a single high-affinity site and that both 10 and 500 nmol/L cocaine inhibit sodium-dependent alanine uptake. The purpose of this study was to characterize cocaine binding to human placental basal plasma membrane and to determine the effects of cocaine on basal vesicle uptake of alanine and leucine.


METHODS
Basal vesicles were isolated from the placentas of uncomplicated human pregnancies with no history of cocaine use. The binding of tritiated cocaine to basal vesicle membrane and the uptakes of tritiated cocaine, alanine, and leucine were determined with filtration assays. Alanine and leucine uptakes were measured in the presence and absence of sodium and 10 and 500 nmol/L cocaine. Cocaine binding was characterized with Scatchard analyses, and uptakes were compared by means of Student t tests.


RESULTS
Tritiated cocaine bound to basal membrane at two separate high-affinity sites. Sodium-dependent alanine uptake was significantly inhibited only by 500 nmol/L cocaine. Sodium-independent amino acid uptake was unaffected by cocaine.


CONCLUSIONS
Cocaine may interfere with fetal growth by impairing the activity of sodium-dependent amino acid transporters in both the microvillous and basal membrane. These membranes may be differentially sensitive to the effects of cocaine on such transporters.
Dicke
J M
JM
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO.
Verges
D K
DK
Polakoski
K L
KL
D000328:Adult; D000409:Alanine / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000378:metabolism* / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy
D007930:Leucine; D003042:Cocaine; D000409:Alanine