Dicke J M, Verges D K, Polakoski K L
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO.
Am J Obstet Gynecol. 1994 Aug;171(2):485-91. doi: 10.1016/0002-9378(94)90287-9.
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.
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.
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.
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.
先前的研究表明，可卡因在人胎盘微绒毛膜囊泡上的单一高亲和力位点结合，且10和500 nmol/L的可卡因均可抑制钠依赖性丙氨酸摄取。本研究的目的是描述可卡因与人胎盘基底质膜的结合情况，并确定可卡因对基底囊泡摄取丙氨酸和亮氨酸的影响。
从无可卡因使用史的正常妊娠孕妇的胎盘中分离出基底囊泡。用过滤分析法测定氚标记可卡因与基底囊泡膜的结合以及氚标记可卡因、丙氨酸和亮氨酸的摄取。在有钠和无钠以及存在10和500 nmol/L可卡因的情况下测量丙氨酸和亮氨酸的摄取。用Scatchard分析对可卡因结合进行表征，并通过学生t检验比较摄取情况。
氚标记可卡因在两个不同的高亲和力位点与基底膜结合。仅500 nmol/L的可卡因显著抑制钠依赖性丙氨酸摄取。非钠依赖性氨基酸摄取不受可卡因影响。
可卡因可能通过损害微绒毛膜和基底膜中钠依赖性氨基酸转运体的活性来干扰胎儿生长。这些膜对可卡因对此类转运体的影响可能具有不同的敏感性。
