Cocaine inhibits alanine uptake by human placental microvillous membrane vesicles.
OBJECTIVE
The aim of this study was to determine the effects of cocaine on alanine uptake by human placental microvillous membrane vesicles and to characterize cocaine binding to the microvillous membrane.


METHODS
Microvillous vesicles were isolated from the placentas of 10 human pregnancies with no history of cocaine use. The binding of tritiated cocaine to microvillous vesicle membrane and uptake of tritiated cocaine and tritiated alanine were determined with the use of filtration assays. Scatchard analyses were used to characterize cocaine binding. Sodium-independent and sodium-dependent uptake of tritiated alanine was measured in the presence and absence of (-)cocaine and its stereoisomer (+)cocaine. Uptakes were compared with the use of Student t tests.


RESULTS
Specific tritiated cocaine binding accounted for approximately 96% of total binding at a single-component high-affinity site in the microvillous membrane. The mediated sodium-dependent component of alanine uptake was significantly (p < 0.01) reduced in the presence of (-)cocaine but was unaffected by (+)cocaine.


CONCLUSIONS
Cocaine may contribute to fetal growth restriction by interfering with the normal activity of placental amino acid transporters necessary to maintain the nutrient gradients associated with normal fetal growth.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO.
J M
JM
Dicke
D K
DK
Verges
K L
KL
Polakoski
D000328:Adult; D000409:Alanine / Q000493:pharmacokinetics*; D001665:Binding Sites / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects* / Q000378:metabolism; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D009994:Osmolar Concentration; D011247:Pregnancy; D012964:Sodium / Q000502:physiology; D013997:Time Factors
D012964:Sodium; D003042:Cocaine; D000409:Alanine