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L-Arginine Transport across the Basal Plasma Membrane of the Syncytiotrophoblast of the Human Placenta from Normal and Preeclamptic Pregnancies

Academic Unit of Child Health, University of Manchester, St. Mary’s Hospital (P.F.S., J.D.G., C.P.S., S.W.D.), Manchester, United Kingdom M13 0JH; Nuffield Department of Obstetrics and Gynecology, John Radcliffe Hospital, University of Oxford (P.T.-Y.A.), Oxford, United Kingdom OX3 9DU; and Department of Human Anatomy and Genetics, University of Oxford (M.R.), Oxford, United Kingdom OX1 3QX

Address all correspondence and requests for reprints to: Dr. P. F. Speake, Human Development and Reproductive Health Academic Group, Academic Unit of Child Health, University of Manchester, St. Mary’s Hospital, Hathersage Road, Manchester, United Kingdom M13 0JH. E-mail: paul.speake{at}man.ac.uk.

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 [³H]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.

This work was supported by the British Heart Foundation and the Wellcome Trust.

Abbreviations: BM, Basal plasma membrane; CAT, cationic amino acid transporter; CBM, BM from control placenta; eNOS, endothelial NOS; EVB, extravesicular buffer; h, human; MVM, microvillous membrane; NO, nitric oxide; NOS, NO synthase; PE, preeclamptic placenta; qRT-PCR, quantitative RT-PCR; V_max, maximum velocity.

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