Taurine transport into fetal cord blood cells: inhibition by cyclosporine A.
OBJECTIVE
Pregnant women undergoing long-term organ transplant treatment have an increased incidence of delivering infants with intrauterine growth restriction (IUGR). Cyclosporine A is used as an immunosuppressant in such women and indirect evidence suggests that IUGR might result from an effect of cyclosporine A on amino acid transport by the placenta. In this study we tested the hypothesis that the transport of an essential amino acid, taurine, by fetal tissue other than the placenta is modulated by cyclosporine A.


METHODS
Cord blood cells (CBCs) were used to test this hypothesis as an easily obtainable fetal tissue. Transport of taurine into CBCs was measured using standard tracer flux assays.


RESULTS
Uptake of [(3)H] taurine by CBCs was linear over 15 minutes (76.2 +/- 16.6 fmol/10(6) cells/min, mean +/- SEM, n = 6) and inhibitable by 10 mM beta-alanine, a substrate of the system-beta taurine transport protein (6.7 +/- 1.0 fmol/10(6) cells/min, n = 6, P <.05, paired Student t test). Pre-incubation with cyclosporine A (5 microM) inhibited [(3)H] taurine uptake by 29.3%-5.3% (n = 8, P <.05, paired Student t test).


CONCLUSIONS
These data show that amino acid transport via system-beta can be measured in CBCs and may be a useful model for amino acid transport studies in fetal cells. We also show that system-beta was inhibited by the immunosuppressant, cyclosporine A. This suggests that the increased incidence of IUGR reported in mothers treated with cyclosporine A may be due partially to effects on taurine uptake into fetal cells outside the placenta.
Speake
Paul F
PF
Human Development and Reproductive Health Academic Group, Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom. paul.speake@man.ac.uk
Zipitis
Christos S
CS
Houston
Angela
A
D'Souza
Stephen
S
D001692:Biological Transport / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007700:Kinetics; D011247:Pregnancy; D013654:Taurine / Q000378:metabolism*; D014316:Tritium
D014316:Tritium; D013654:Taurine; D016572:Cyclosporine