Placental aminopeptidase A as a possible barrier of angiotensin II between mother and fetus.
Aminopeptidase A (AP-A EC 3.4.11.7), which is a membrane-bound zinc metalloprotease, is present in the placenta. AP-A selectively hydrolyzes N-terminal glutamyl and aspartyl residues and cleaves angiotensin II to form angiotensin III. To determine the role of placental aminopeptidase A under physiological and pathological conditions, we evaluated its immunolocalization and enzymatic activities in the placenta. AP-A was localized in the basal zone of the syncytiotrophoblast, in the membranes of the cytotrophoblast, and in fetal arterioles and venules within the stem villi. AP-A activity in the microsomal fraction of placental villi seemed to be remained essentially constant throughout gestation. The renin-angiotensin system is considered to be accelerated in pre-eclampsia. This AP-A activity was higher in pre-eclampsia (2.86+/-0.30 nmol beta NA/mg protein/h) than in uncomplicated pregnancy from 28 to 41 weeks of gestation (2.08+/-0.18 nmol beta NA/mg protein/h). Angiotensin II evoked AP-A activity in first trimester trophoblast, and Losartan and PD 123177 in combination significantly inhibited this induction of AP-A activity. The results of immunohistochemical evaluation and enzymatic activity suggested that placental aminopeptidase A may play a role as a component of the barrier of angiotensin II between mother and fetus.
Hariyama
Y
Y
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.  
Itakura
A
A
Okamura
M
M
Ito
M
M
Murata
Y
Y
Nagasaka
T
T
Nakazato
H
H
Mizutani
S
S
D000328:Adult; D000626:Aminopeptidases / Q000032:analysis / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism; D001160:Arterioles / Q000201:enzymology; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000098:blood supply; D005865:Gestational Age; D043384:Glutamyl Aminopeptidase; D006801:Humans; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000502:physiology; D014018:Tissue Distribution; D014327:Trophoblasts / Q000201:enzymology; D014699:Venules / Q000201:enzymology
D000804:Angiotensin II; D000805:Angiotensin III; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase