M. Ramirez et al., HYPOXANTHINE UPTAKE AT THE FETAL SIDE OF HUMAN PLACENTA PROCEEDS THROUGH A NUCLEOBASE-PREFERRING CARRIER AND A NONSATURABLE PROCESS, Placenta, 18(4), 1997, pp. 327-332
Uptake and metabolism of hypoxanthine by human placenta were studied u
sing the single-circulation paired-tracer technique. In isolated cotyl
edons perfused through the fetal (basal) circulation, at mean pressure
s of 31.7 +/- 4.0 mmHg and mean flow rates maintained at 5.5 +/- 0.15
ml/min, the [H-3]hypoxanthine uptake was 36 +/- 2.4 per cent (16.5 +/-
1.1 pmol/g wet weight). Hypoxanthine uptake was significantly inhibit
ed 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 an
alysis of hypoxanthine uptake showed it to be partially mediated by a
saturable (apparent K-m = 12.1 +/- 1.85 mu m; F-max=7.1 +/- 0.52 nmol/
min) and Na+-dependent mechanism. A greater fraction of hypoxanthine i
nflux proceeded through a non-saturable process. Thin layer chromatogr
aphic analysis of venous perfusate after the intra-arterial injection
of [H-3]hypoxanthine showed a negligible degradation of nucleobase. Th
ese overall results show that hypoxanthine uptake at the fetal side of
human placenta occurs by a saturable plus a non-saturable process. Th
e carrier showed specificity for nucleobases and high affinity-low cap
acity for hypoxanthine. Since the fetal blood concentration of hypoxan
thine is normally low, its uptake would be mediated by the high affini
ty transport system. Because the non-saturable mechanism can be operat
ive at high concentrations of hypoxanthine, it may have primary import
ance to clear the nucleobase coming from the fetus during intrauterine
hypoxia. (C) 1997 W. B. Saunders Company Ltd.