Hypoxanthine uptake at the fetal side of human placenta proceeds through a nucleobase-preferring carrier and a non-saturable process.
Uptake and metabolism of hypoxanthine by human placenta were studied using the single-circulation paired-tracer technique. In isolated cotyledons perfused through the fetal (basal) circulation, at mean pressures of 31.7 +/- 4.0 mmHg and mean flow rates maintained at 5.5 +/- 0.15 ml/min, the [3H]hypoxanthine uptake was 36 +/- 2.4 per cent (16.5 +/- 1.1 pmol/g wet weight). Hypoxanthine uptake was significantly inhibited by unlabelled (mM) hypoxanthine (0.5), adenine (0.5), guanine (0.5) and papaverine (15.0), but was unaffected by nitrobenzylthioinosine (0.01). Adenosine failed to inhibit hypoxanthine uptake. The kinetic analysis of hypoxanthine uptake showed it to be partially mediated by a saturable (apparent K(m) = 12.1 +/- 1.85 microns; Jmax = 7.1 +/- 0.52 nmol/min) and Na(+)-dependent mechanism. A greater fraction of hypoxanthine influx proceeded through a non-saturable process. Thin layer chromatographic analysis of venous perfusate after the intra-arterial injection of [3H]hypoxanthine showed a negligible degradation of nucleobase. These overall results show that hypoxanthine uptake at the fetal side of human placenta occurs by a saturable plus a non-saturable process. The carrier showed specificity for nucleobases and high affinity-low capacity for hypoxanthine. Since the fetal blood concentration of hypoxanthine is normally low, its uptake would be mediated by the high affinity transport system. Because the non-saturable mechanism can be operative at high concentrations of hypoxanthine, it may have primary importance to clear the nucleobase coming from the fetus during intrauterine hypoxia.
Ramírez
M
M
Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile.
Acevedo
C G
CG
Rojas
S
S
Bravo
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I
D000225:Adenine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D001692:Biological Transport; D001783:Blood Flow Velocity; D005260:Female; D005333:Fetus / Q000378:metabolism; D006147:Guanine / Q000494:pharmacology; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism* / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D011247:Pregnancy; D012964:Sodium / Q000494:pharmacology; D014316:Tritium
D014316:Tritium; D019271:Hypoxanthine; D006147:Guanine; D012964:Sodium; D010208:Papaverine; D000225:Adenine; D000241:Adenosine