Transport and metabolism of adenosine in the perfused guinea‐pig placenta.

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Abstract
1. Uptake and metabolism of adenosine were investigated from both maternal (M) and fetal (F) circulations of the isolated, dually perfused guinea-pig placenta by using a single-circulation paired-tracer ([14C]sucrose as extracellular reference, and [3H]adenosine) dilution technique. 2. Maximal [3H]adenosine uptakes (percentage of dose) from adenosine-free perfusates were 75 .+-. 1 and 87 .+-. 2% (mean .+-. S.E. of mean) at maternal and fetal blood-tissue interfaces respectively. Rapid backflux (percentage of influx) of tritium (labelled adenosine and/or adenosine derivatives) from the placental tissue into the ipsilateral circulation was higher at the fetal (24 .+-. 2%) than at the maternal side (11 .+-. 2%). 3. Tritium uptakes were reduced to 50 .+-. 4 (M) and 60 .+-. 6% (F) when the perfusion medium contained 100 .mu.M-unlabelled adenosine; backflux was highly stimulated (44% M and 84% F). Neither uptake nor backflux were affected by inosine, uridine, adenine or hypoxanthine present in the perfusion medium (1 mM). 4. Tissue sequestration of tritium (5-6 min) was approximately 60% of the injected dose when perfusates were adenosine-free and 20% or less in the presence of 100 .mu.M-adenosine. 5. Cellular uptake of [3H]adenosine at both sides of the placenta was markedly reduced by the nucleoside transport inhibitors dipyridamole (DIP, 10 .mu.M) and nitrobenzylthioinosine (NBMPR, 5 .mu.M). 6 Thin-layer chromatographic separation of [3H]inosine, [3H]hypoxanthine and [3H]phosphorylated derivatives in venous effluents following a bolus arterial injection of [3H]adenosine showed a greater fraction of metabolites at the fetal side (about 0.75) than at the maternal side (about 0.50). The percentage of [3H]inosine increased when perfusates contained 100 .mu.M-adenosine and the effect was more marked in the fetal circulation. In the presence of DIP and NBMPR the fractional recovery of 3H-labelled metabolites was greatly reduced. 7. During steady-state perfusion of [3H]adenosine (100 .mu.M) a maintained (5-60 min) tritium uptake of about 55% was observed and all the effluent activity was 3H-labelled metabolites ([3H]adenosine was only 2.8 .+-. 0.2%). Under these conditions high-performance liquid chromatography (HPLC) showed that effluents contained xanthine and urate at 16 .+-. 1 and 23 .+-. 2 .mu.M respectively. 8. Transplacental transfer (6 min) of tritiated compounds (of which only 10-20% was [3H]adenosine) was often less than that of the extracellular marker [14C]sucrose in both maternal-to-fetal and fetal-to-maternal directions. 9. The present data demonstrate DIP- and NBMPR-sensitive carrier-mediated adenosine uptake at the brush-border side of the syncytiotrophoblast (maternal-facing) and at the fetal side. In the latter case the role of the basal syncytial membrane and the fetal endothelium could not distinguished. Rapid metabolism of adenosine also occurs at both blood-tissue interfaces. The placenta may therefore be involved in the regulation of adenosine-related functions in mother and fetus during pregnancy.