Transport and metabolism of adenosine in the perfused guinea-pig placenta.
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 microM-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 microM-adenosine. 5. Cellular uptake of [3H]adenosine at both sides of the placenta was markedly reduced by the nucleoside transport inhibitors dipyridamole (DIP, 10 microM) and nitrobenzylthioinosine (NBMPR, 5 microM). 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 microM-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 microM) 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 microM 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Wheeler
C P
CP
Department of Physiology, King's College London, University of London.
Yudilevich
D L
DL
D000241:Adenosine / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood; D007288:Inosine / Q000097:blood; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014316:Tritium; D014527:Uric Acid / Q000378:metabolism
D007042:Hypoxanthines; D014316:Tritium; D014527:Uric Acid; D019271:Hypoxanthine; D013868:Thioinosine; D007288:Inosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine