The effect of cyclosporine on taurine transport in human cord blood cells

University of Central Lancashire / University of Liverpool (2002) J Physiol 543P, S095

Communications: The effect of cyclosporine on taurine transport in human cord blood cells

P.F. Speake, C. Zipitis and S.W. D'Souza

Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK

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Cyclosporine has been used in long-term organ transplant treatment and there are reports of an increased occurrence of intrauterine growth retardation (IUGR) in pregnancies in such patients (Pickrell et al. 1988; Cockburn & Krupp, 1989). Indirect evidence suggests that this might result from an inhibitory effect of cyclosporine on taurine uptake by the placenta (Ramamoorthy et al. 1992). Here we investigated taurine transport by peripheral blood mononuclear cells (PBMs) enriched from cord blood (CB), an alternative and easily obtainable fetal tissue to placental tissue. We determined whether cyclosporine inhibited taurine uptake by these cells.

CB was obtained from placentas from normal term pregnancies in accordance with local ethical approval. PBMs were enriched by dilution with Hanks’ biological salt solution (HBSS, containing (mM): NaCl 137, KCl 5.4, KH2PO4 0.4, Na2HPO4 0.34, NaHCO3 4.2 and glucose 5.6) and centrifuged at 400 g for 30 min (modified from Wan et al. 1999). [3H] taurine uptake was measured with or without 10 mM β-alanine at 37 °C with or without pre-incubation with cyclosporine (5 mM), 37°C for 10 min using methods similar to those previously described (Ayuk et al. 2000). Data are expressed as means ± S.E.M.; n = number of placentas from which CB samples were taken.

Uptake of [3H] taurine by CB PBMs was linear over 15 min (5.49 ± 0.92 fmol (106 cells)-1 min-1, n = 6), inhibitable by β-alanine (0.22 ± 0.09 fmol (106 cells)-1 min-1, n = 6 P < 0.05, Student’s paired t test). Pre-incubation with cyclosporine (5 mM) inhibited [3H] taurine uptake by 29.3 ± 5.3 % (n = 8, P < 0.05, Student’s paired t test). There was no effect on the uptake of [3H] taurine by methanol, the vehicle used to dissolve cyclosporine.

In conclusion, the effect of β-alanine on taurine uptake into CB PBMs suggests that this was mediated by system β, although further characterisation is required. The inhibitory effect of cyclosporine on taurine transport in CBCs was comparable to that seen in choriocarcinoma cells (Ramamoorthy et al. 1992). Thus the increased incidence of IUGR previously reported in mothers being treated with cyclosporine A might be due partially to effects on taurine uptake into fetal and placental tissues.

We acknowledge support from The Wellcome Trust, Action Research Endowment Fund, Professor Colin Sibley and Dr Sue Greenwood.

All procedures accord with current local guidelines.



Where applicable, experiments conform with Society ethical requirements.

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