Initiating and responsible enzyme of arginine vasopressin degradation in human placenta and pregnancy serum.
The hydrolysis of arginine vasopressin (AVP) by human placental subcellular fractions and pregnancy sera was studied in the presence of selective inhibitors and the antibody against pregnancy serum oxytocinase (P-LAP) (EC 3.4.11.3) by measuring liberated amino acids by high-performance liquid chromatography (HPLC). AVP degradation by placental subcellular fractions and pregnancy sera was inhibited by bestatin. The IC50 values of bestatin on AVP degradation by placental subcellular fractions and pregnancy sera were similar to that of this inhibitor on the P-LAP measured by L-Leu-p-nitroamnilide as a substrate (LAP activity), which we reported previously. Our immunotitration study clearly showed that the initiating and responsible protease in AVP degradation in human placenta and pregnancy serum is P-LAP. Since N-benzylcarbonyl-valyl-prolinal (Z-Val-prolinal), a selective inhibitor of post-proline endopeptidase, and phosphoramidon, a putative endopeptidase-24.11 inhibitor, could not significantly influence the degradation of AVP by placental microsomal fractions. Neither enzyme seems to be actively involved in AVP degradation.
Mizutani
S
S
Department of Obstetrics and Gynecology, Nagoya University School of medicine, Japan.
Safwat
M A
MA
Goto
K
K
Tsujimoto
M
M
Nakazato
H
H
Itakura
A
A
Mizuno
M
M
Kurauchi
O
O
Kikkawa
F
F
Tomoda
Y
Y
D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000378:metabolism*; D002458:Cell Fractionation; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008623:Mercaptoethanol / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy / Q000097:blood*; D011480:Protease Inhibitors / Q000494:pharmacology
D004151:Dipeptides; D006020:Glycopeptides; D011480:Protease Inhibitors; D001127:Arginine Vasopressin; D008623:Mercaptoethanol; C042268:N-benzyloxycarbonylvalylprolinal; D004492:Edetic Acid; D010122:Cystinyl Aminopeptidase; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon