TRANSPORT AND METABOLISM OF ADENOSINE IN THE PERFUSED HUMAN PLACENTA

Uptake and metabolism of adenosine by human placenta mere studied usin g the single-circulation paired-tracer technique. When isolated cotyle dons were perfused through the fetal (basal) circulation at mean press ures of 36 +/- 3.3 mmHg and mean from rates of 6.6 +/- 0.3 ml/min the maximal [H-3]adenosine uptake was 51.3 +/- 3.9 per cent. The uptake wa s not changed when the vascular resistance was pharmacologically incre ased. Adenosine uptake was significantly inhibited by adenosine, inosi ne and nitrobenzylthioinosine (NBMPR), but was unaffected by hypoxanth ine. The Kinetic analysis of adenosine transport showed it to be a sat urable and Na+-independent process, with a K-m of 60.8 mu M and a J(ma x) of 0.148 mu mol/min. Thin layer chromatographic analysis showed tha t about 65 per cent of [H-3]adenosine was metabolized (10-30 sec) in a single passage through the fetoplacental circulation. [H-3]hypoxanthi ne and [H-3]adenine were the major products recovered in the venous pe rfusate. In the presence of NBMPR the fractional recovery of [H-3]aden ine and [H-3]phosphorylated derivatives was reduced while that of [H-3 ]hypoxanthine was increased. These overall results show that the uptak e of adenosine is a Na+-independent, NBMPR-sensitive, carrier-mediated process, which appears to be specific for nucleosides, and suggests t hat metabolization of adenosine proceeds both intra- and extracellular ly.