Amino acid (AA) transport from mother to fetus depends on active transport into the placenta, followed by efflux into the fetus. It is not clear whether the efflux is by passive diffusion, or is mediated by Naindependent transporters. We measured transport into and across the placenta of 3 nonmetabolizable AAs: 3Hαmethylaminoisobutyric acid (MeAIB),3 Hαaminoisobutyric acid (AIB), and14 Claminocyclopentanelcarboxylic acid (ACP). MeAIB is specific for Nadependent transport system A, whereas AIB and ACP have affinity for more than one transporter, including Naindependent systems. These AAs were injected intravenously over 1 minute into 5 pregnant sheep (mean gestational age 134± 4 days), equipped with catheters for sampling uterine arterial and venous, and umbilical arterial and venous blood. Specimens were collected in rapid succession, and analyzed for AA radioactivity. Fetal ethanol infusion was used for measuring uterine and umbilical blood flows. At 3 hours after the bolus, the sheep were euthanized to determine the placental concentration of the injected isotopes. MeAIB clearance from uterine circulation to pregnant uterus was approximately 80 times greater than MeAIB clearance from placenta to fetus (15.78 ± 2.98 vs. 0.20 ± 0.09 mL/kg fetus/min; n = 3). The concentration of MeAIB in the placenta was 46 times the concentration in umbilical venous blood. In contrast, the clearance of AIB and ACP from uterine circulation to pregnant uterus was 3.2 times and 1.6 times greater, respectively, than the clearance from placenta to fetus (AIB: 20.36 vs. 6.45 mL/kg fetus/min; n = 2, and ACP: 14.14 ± 0.83 vs. 8.70 ± 1.12 mL/kg fetus/min; n = 5). The placental concentrations of these two AAs were 15 and 2.5 times, respectively, the concentrations in umbilical venous blood. Thus, MeAIB was taken up by the placenta, with minimal release into fetal circulation, whereas AIB and ACP were transferred from the placenta into the fetal circulation in significant amounts. This indicates that Naindependent transport systems play an important role in the efflux of AAs from placenta to fetus.
