Transport and metabolism of adenosine in the perfused human placenta

Uptake and metabolism of adenosine by human placenta were studied using the single-circulation paired-tracer technique. When isolated cotyledons were perfused through the fetal (basal) circulation at mean pressures of 36 +/- 3.3 mmHg and mean flow rates of 6.6 +/- 0.3 ml/min the maximal [3H]adenosine uptake was 51.3 +/- 3.9 per cent. The uptake was not changed when the vascular resistance was pharmacologically increased. Adenosine uptake was significantly inhibited by adenosine, inosine and nitrobenzylthioinosine (NBMPR), but was unaffected by hypoxanthine. The kinetic analysis of adenosine transport showed it to be a saturable and, Na(+)-independent process, with a Km of 60.8 microM and a Jmax of 0.148 mumol/min. Thin layer chromatographic analysis showed that about 65 per cent of [3H]adenosine was metabolized (10-30 sec) in a single passage through the fetoplacental circulation. [3H]hypoxanthine and [3H]adenine were the major products recovered in the venous perfusate. In the presence of NBMPR the fractional recovery of [3H]adenine and [3H]phosphorylated derivatives was reduced while that of [3H]hypoxanthine was increased. These overall results show that the uptake of adenosine is a Na(+)-independent, NBMPR-sensitive, carrier-mediated process, which appears to be specific for nucleosides, and suggests that metabolization of adenosine proceeds both intra- and extracellularly.