Asymmetrical transfer of α-aminoisobutyric acid (AIB), leucine and lysine across the in vitro perfused human placenta

Schneider, H.; Proegler, Mariette; Sodha, R. J.; Dancis, Joseph

doi:10.1016/0143-4004(87)90017-8

Cited by 40 publications

(17 citation statements)

References 21 publications

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“…At least five different transport systems for neutral amino acids have been identified in the human syncytiotrophoblast using villous tissue fragments (12), in vitro perfused placenta (13)(14)(15), and cultured trophoblast cells (16) and cell lines (17) as well as in plasma membrane vesicles (Table 1). System A mediates the transport of zwitterionic amino acids with small side chains and has not yet been characterized at the molecular level (6).…”

Section: Placental Amino Acid Transportersmentioning

confidence: 99%

Amino Acid Transporters in the Human Placenta

2001

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The following two reviews deal with the important topic of the physiology of amino acid metabolism in the maternal-placental-fetal unit. Dr. Jansson discusses the biology of amino acid transporters and Dr. Cetin reviews studies of amino acid transport and metabolism in experimental animals and humans. Recent work on the relation between abnormalities of amino acid transport and intrauterine growth retardation underline the importance of this topic and of these timely reviews. Alvin Zipursky Editor-in-ChiefAmino Acid Transporters in the Human Placenta THOMAS JANSSONPerinatal Center, Department of Physiology and Pharmacology, Göteborg University, Sweden Amino acid transport across the human placenta is active, mediated by specific transporters in syncytiotrophoblast plasma membranes. Using functional criteria such as substrate specificity and sodium dependence, approximately 15 transport systems have been identified in the human placenta. Recently, the area of molecular biology of amino acid transporters has evolved rapidly and at least 25 cDNA clones coding for mammalian amino acid transporters or transporter subunits have been identified. The primary objective of this review is to integrate the available functional data on placental amino acid transport systems with recent molecular information on mammalian amino acid transporters. Furthermore, models for the mechanisms for net materno-fetal transfer of amino acids are discussed. Finally, the evidence to suggest that alterations in placental amino acid transport systems may play a crucial role in the regulation of fetal growth are presented briefly. The plasma concentrations of most amino acids are higher in the fetus than in the mother (1), suggesting an active transport of amino acids across the human placenta. There are only two cell layers positioned between the maternal and fetal circulation in the human placenta: the syncytiotrophoblast and the fetal capillary endothelium. The endothelium has been shown to be of the continuous type, closely resembling other continuous nonbrain capillaries (2). This endothelial type allows for relatively unrestricted passage of amino acids through pores within the interendothelial cleft (3) and is therefore unlikely to represent a significant barrier to transport of amino acids. Instead, the transport across the polarized plasma membranes of the syncytiotrophoblast probably represents the limiting step in transplacental amino acid transfer. Consequently, isolated microvillous and basal syncytiotrophoblast membranes studied in vitro are particularly valuable experimental systems in elucidating the cellular mechanisms of amino acid transport across the placenta.Amino acids are transported across plasma membranes mediated by transporter proteins. As a result of pioneer work some 50 years ago, in particular originating from Christensen et al. (4), mammalian amino acid transport systems were identified and characterized according to functional criteria such as substrate specificity and sodium dependence.

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Section: Placental Amino Acid Transportersmentioning

confidence: 99%

Amino Acid Transporters in the Human Placenta

2001

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“…We now report that over the gestational age range of 20-37 wk, under relativel y undisturbed fetomat ernal conditions (fetal blood sampling) , human placental glycine transfer is limited , with a glycinelleucine ratio = 0.16 ± 0.02. We Amino acid transport properties for the human placenta in late gestation have been studied extensively in vitro utilizing two different approaches: isolated microvesicles from either the maternal or basal surfaces (1,2) or the perfused placental lobule or entire placenta (3,4). The properties of the perfused placenta with respect to amino acid transport have been somewhat surprising in that very little difference in placental clearance for amino acids such as glycine and leucine has been found (5).…”

Section: L-[i-mentioning

confidence: 99%

In Vivo Placental Transport of Glycine and Leucine in Human Pregnancies

et al. 1995

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L-[I-13 C]Glycine and L-[I-13 C]leucine were infused as a bolus into 12 pregn ant patients carrying normal fetuses before fetal blood sampling at gestational ages ranging from 20 to 37 wk. Maternal venous samples were obtained every 2-3 min for 15 min after the bolus infusion . Fetal samples were obtained from the umbilical vein within 15 min of the bolus. Amino acid plasma enrichments (molar percent enrichment) were determined by gas chromatography-mass spectroscopy and their concentrations by ion exchang e chromatography. The ratios of glycine and leucine transfer were assessed from fetal/maternal enrichment ratios for each amino acid. We now report that over the gestational age range of 20-37 wk, under relativel y undisturbed fetomat ernal conditions (fetal blood sampling) , human placental glycine transfer is limited , with a glycinelleucine ratio = 0.16 ± 0.02. We

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“…The in vitro perfusion model provided valuable information on transplacental transport of nutrients such as amino acids (Schneider et al 1979;Schneider et al 1987), fatty acids (Dancis et al 1974;Dancis et al 1973), hormones (insulin (Boskovic et al 2003;Menon et al 1990), vitamins (biotin, thiamin) (Schenker et al 1990;Schenker et al 1992) and various drugs, such as anesthetics drugs (Ala-Kokko et al 1995;Giroux et al 1997), antidiabetic related drugs (Elliott et al 1991;Elliott et al 1994;Holmes et al 2006;Nanovskaya et al 2006;Kovo et al 2008a;Kovo et al 2008b), HIV protease inhibitors (Olivero et al 1999;Forestier et al 2001), antiepileptic drugs (Pienimaki et al 1997;Myllynen et al 2003), abused drugs (Malek et al 1995;Nanovskaya et al 2008) and antibiotics (Polachek et al 2005 (Bourget et al 1995;Myren et al 2007). In addition, we can learn from such perfusion experiments about the effect of exogenous compounds on the placental transfer of endogenous compounds.…”

Section: Placental Transfer Of Substancementioning

confidence: 99%

In Vitro Models Using the Human Placenta to Study Fetal Exposure to Drugs

Kovo

Golan

2008

Clinical medicine. Reproductive health

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Over the recent years there has been a gradual rise in the use of pharmaceuticals during pregnancy. Knowledge on placental drug transfer and metabolism has increased during the past decades as well. Investigation of the transplacental transfer of any therapeutically useful drug is essential to the understanding of its metabolic processes and is a prerequisite for its use during pregnancy. The purpose of this review is to give insight on the various techniques that have been developed to evaluate transplacental transfer of drugs and xenobiotics.

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Asymmetrical transfer of α-aminoisobutyric acid (AIB), leucine and lysine across the in vitro perfused human placenta

Cited by 40 publications

References 21 publications

Amino Acid Transporters in the Human Placenta

Amino Acid Transporters in the Human Placenta

In Vivo Placental Transport of Glycine and Leucine in Human Pregnancies

In Vitro Models Using the Human Placenta to Study Fetal Exposure to Drugs

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