Physiological importance of system A-mediated amino acid transport to rat fetal development.
Fetal growth and development are dependent on the delivery of amino acids from maternal amino acid pools to the fetal blood. This is accomplished via transfer across the apical and basal plasma membrane of the placental syncytiotrophoblast. The aim of this study was to determine whether inhibition of system A (amino acid transporter) was associated with a decrease in fetal weight in the rat. System A is a ubiquitous Na(+)-dependent amino acid transporter that actively transports small zwitterionic amino acids. In brief, system A was inhibited by infusing a nonmetabolizable synthetic amino acid analog, 2-(methylamino)isobutyric acid from days 7-20 of gestation. On day 20, the rats were killed and tissues (maternal liver, fetuses, and placentas) were collected for analysis. The degree of system A inhibition was determined, as was the impact of said inhibition on fetal and maternal weights, system A-mediated placental transport, and placental system A-mediated transporter expression. Our results suggest that when system A is inhibited, fetal weight is diminished [control group: -3.55 +/- 0.04 g (n = 113), experimental group: -3.29 +/- 0.04 g (n = 128)], implying an integral role for system A transport in fetal growth and development in the rat.
Cramer
Stuart
S
Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Beveridge
Mark
M
Kilberg
Michael
M
Novak
Donald
D
D026924:Amino Acid Transport System A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG / Q000032:analysis; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D001786:Blood Glucose; D015152:Blotting, Northern; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins; D015151:Immunoblotting; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D010927:Placental Insufficiency / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000032:analysis; D027981:Symporters; D014316:Tritium; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D026924:Amino Acid Transport System A; D027322:Amino Acid Transport System X-AG; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C412568:Slc38a2 protein, rat; D027981:Symporters; D014316:Tritium; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D001224:Aspartic Acid