L-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and preeclamptic pregnancies.
Cord blood levels of nitrate/nitrite, as a measure of nitric oxide (NO), are generally increased in preeclampsia. As L-arginine is the precursor for NO synthesis, we hypothesized that L-arginine transport across the syncytiotrophoblast basal plasma membrane (BM) of placentas from preeclamptic patients is also increased. Glutamine-sensitive and -insensitive [(3)H]L-arginine uptakes into BM vesicles were measured and expressed as femtomoles per milligram of protein per minute. Total L-arginine uptake was 418 +/- 15 (mean +/- SEM; n = 9) in BM from control placentas (CBM) and 495 +/- 27 (n = 7) in BM from preeclamptic placentas (PE BM; P < 0.05, by two-tailed t test). Glutamine insensitive (system y(+)) uptake was 45 +/- 3 (n = 6) in CBM, with a significantly higher uptake of 97 +/- 23 (n = 5) into PE BM (P < 0.05, by two-tailed t test). There was no significant difference in glutamine-sensitive uptake between the two groups. The expression of mRNA for human cationic amino acid transporter (hCAT) 1, 2, and 4 (system y(+) genes) and 4F2hc (heavy chain of system y(+)L) was not different in homogenates of whole placenta from the two groups. Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM. These data suggest increased activity of the BM system y(+) cationic amino acid transporter in preeclampsia. If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS.
Speake
P F
PF
Academic Unit of Child Health, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom M13 0JH. paul.speake@man.ac.uk
Glazier
J D
JD
Ayuk
P T-Y
PT
Reade
M
M
Sibley
C P
CP
D'Souza
S W
SW
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D001693:Biological Transport, Active; D015153:Blotting, Western; D027201:Cationic Amino Acid Transporter 1 / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D003720:Densitometry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*
D027201:Cationic Amino Acid Transporter 1; D012333:RNA, Messenger; C420825:SLC7A1 protein, human; D001120:Arginine; D000469:Alkaline Phosphatase