Degradation of oxytocin by the human placenta: effect of selective inhibitors.
The hydrolysis of oxytocin by human placental subcellular fractions was studied in the presence of selective inhibitors by measuring liberated amino acids by high performance liquid chromatography (HPLC). Oxytocin degradation by microsomal and lysosomal fractions was inhibited by bestatin, amastatin and puromycin. The IC50 values of these inhibitors on oxytocin degradation by both fractions were similar to those of these inhibitors on the human placental aminopeptidase M measured by L-Leu-p-nitroanilide as a substrate (LAP activity), which we reported previously. However, purified aminopeptidase M from human placental microsomal fractions could not liberate any amino acid from oxytocin. Since phosphoramidon (1 mumol/l), a putative metalloendopeptidase inhibitor, and N-benzylcarbonyl-valyl-prolinal (Z-Val-prolinal) (14 mumol/l), a selective inhibitor of post-proline endopeptidase, could not significantly influence the degradation of oxytocin by either subcellular fractions, neither enzyme seems to be actively involved in oxytocin degradation. These results strongly suggested the existence of oxytocinase(s) other than the above three enzymes in microsomal and/or lysosomal fractions of human placenta.
Department of Obstetrics and Gynaecology, Nagoya University School of Medicine, Japan.
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Mizutani
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Yokosawa
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Y
Tomoda
D000596:Amino Acids / Q000032:analysis; D000626:Aminopeptidases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018826:CD13 Antigens; D002851:Chromatography, High Pressure Liquid; D010122:Cystinyl Aminopeptidase / Q000032:analysis / Q000502:physiology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007931:Leucyl Aminopeptidase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008861:Microsomes / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D010455:Peptides; D010920:Placenta / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D000085822:Prolyl Oligopeptidases; D011691:Puromycin / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D009842:Oligopeptides; D010455:Peptides; D011691:Puromycin; D010121:Oxytocin; C016977:amastatin; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; D018826:CD13 Antigens; D010122:Cystinyl Aminopeptidase; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon