Effects of low molecular weight peptides and divalent cations on degradation and binding of angiotensin II.
The effects of peptide inhibitors (bestatin and amastatin) and divalent cations (Ca2+ and Co2+) on the velocity of Asp1 liberation from angiotensin II (A-II) by human placental membrane fractions and binding of 125I A-II to human placental membranes were tested at 22 degrees C and 4 degrees C. Asp1 liberation was measured by high performance liquid chromatography. As expected, the degradation and binding of A-II were temperature sensitive, with both being at 4 degrees C than at 22 degrees C. While amastatin (10(-4) M) and bestatin 10(-6) M) significantly reduced the velocity of Asp1 liberation from A-II to about 45%, amastatin (10(-4) M) and bestatin (10(-4) M) increased 125I A-II binding to 125% and 130%, respectively. Ca2+ (10 mM) and Co2+ (10 mM) activated the velocity of Asp1 liberation from A-II to 140% and 120%, respectively at 22 degrees C. Ca2+ (10(-1) M) and Co2+ (10 mM) also enhanced 125I A-II binding about 130%. Previously we showed that the A-II degrading activity found in human placental membrane fractions is mainly due to aminopeptidases A and M. Since amastatin and bestatin are the specific inhibitors for aminopeptidases A and M, and since Ca2+ and Co2+ are the activators for aminopeptidase A and aminopeptidase M, respectively, it is conceivable that the enzymes regulate the levels of A-II and, therefore, that they may play an important role in the binding of A-II to human placental membrane fractions.
Nomura
S
S
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Mizutani
S
S
Kurauchi
O
O
Kasugai
M
M
Narita
O
O
Tomoda
Y
Y
D000328:Adult; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000900:Anti-Bacterial Agents; D002413:Cations, Divalent / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008970:Molecular Weight; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy
D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D010455:Peptides; D000804:Angiotensin II; D003035:Cobalt; C016977:amastatin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex