Bzoskie I, Blount I, Kashiwai K, Humme J, Padbury J F
Department of Pediatrics, Harbor-UCLA Medical Center, UCLA School of Medicine, USA.
Placenta. 1997 Jan;18(1):65-70. doi: 10.1016/s0143-4004(97)90072-2.
The placenta has been shown to be a site of expression of several of the monoamine membrane uptake transporters. However, the development and relative contribution of transport-dependent mechanisms to placental catecholamine clearance in vivo have not been demonstrated. These studies were designed to determine the development of the placental norepinephrine transporter (NET) and the relative contribution of transport dependent mechanisms to whole body and placental catecholamine clearance. Norepinephrine clearance and production rate were determined in 122 +/- 1 day gestation chronically catheterized fetal sheep. Placental clearance was shown to account for over 40 per cent of total intrauterine clearance and, of the clearance in the placenta, nearly 50 per cent was uptake, transport-dependent as shown by specific pharmacologic blockade. NET transport expression was examined by measurement nisoxetine binding in placenta and compared with binding in the frontal cortex of fetal, newborn and adult animals. Nisoxetine is a selective ligand for the norepinephrine transporter. Nisoxetine binding was 20-fold greater in placenta than in frontal cortex. Placental transporter binding decreased modestly in between 99 days gestation and term (145 days) but did not change in frontal cortex. These results suggest that expression of the norepinephrine transporter in the placenta is associated with a significant capacity for neurotransmitter re-uptake in utero. Given the high fetal norepinephrine production rate, this capacity is important for fetal homeostasis. This site of transporter expression may be important in the pathogenesis of derangements in catecholamine production in the fetus and in the adverse effects on the fetus of drugs, such as cocaine, which block catecholamine re-uptake.
胎盘已被证明是几种单胺膜摄取转运体的表达部位。然而，转运依赖机制在体内对胎盘儿茶酚胺清除的发育及相对贡献尚未得到证实。这些研究旨在确定胎盘去甲肾上腺素转运体（NET）的发育情况以及转运依赖机制对全身和胎盘儿茶酚胺清除的相对贡献。在妊娠122±1天、长期插管的胎羊中测定去甲肾上腺素清除率和生成率。胎盘清除率占子宫内总清除率的40%以上，在胎盘中，近50%的清除是摄取，特异性药物阻断表明这是转运依赖的。通过测量胎盘中西酞普兰结合来检测NET转运体表达，并与胎儿、新生儿和成年动物额叶皮质中的结合情况进行比较。西酞普兰是去甲肾上腺素转运体的选择性配体。胎盘中西酞普兰结合比额叶皮质高20倍。胎盘转运体结合在妊娠99天至足月（145天）之间略有下降，但额叶皮质中没有变化。这些结果表明，胎盘中去甲肾上腺素转运体的表达与子宫内神经递质再摄取的显著能力有关。鉴于胎儿去甲肾上腺素生成率高，这种能力对胎儿内环境稳定很重要。转运体表达部位可能在胎儿儿茶酚胺生成紊乱的发病机制以及对胎儿的药物（如可卡因）不良反应中起重要作用，可卡因会阻断儿茶酚胺再摄取。
