Placental leucine aminopeptidase might regulate the effects of oxytocin with resolution in endothelial cells.
BACKGROUND
Oxytocin (OT) is known to cause vascular relaxation via nitric oxide (NO) production and proliferation of endothelial cells. Previously we revealed that human umbilical vascular endothelial cells (HUVECs) expresses placental leucine aminopeptidase (P-LAP)/insulin regulated aminopeptidase (IRAP), which becomes translocation to the cell surface on activation of oxytocin receptor (OTR). However, the physiological roles of P-LAP in HUVECs have not been elucidated.


METHODS
Actions of OT on HUVECs transfected with a copy of the human P-LAP gene were therefore examined with a focus on changes in parameters linked to OTR such as calcium mobilization, NO production and cell proliferation.


RESULTS
Cell surface P-LAP activity was significantly elevated (approximately 3 fold) in P-LAP overexpressing-HUVECs and overexpression of P-LAP resulted in remarkable inhibition of OT effects on HUVECs such as cell proliferation, [Ca2+]i, and NO production.


CONCLUSIONS
These findings suggested that P-LAP on the plasma membrane in HUVECs regulates the effects of OT with resolution around OTR.
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Michiyo
M
Sano
Atsuo
A
Itakura
Mitsuaki
M
Ito
Mikihito
M
Takeuchi
Mayumi
M
Okada
Tomomi
T
Kotani
Shigehiko
S
Mizutani
Fumitaka
F
Kikkawa
D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D010122:Cystinyl Aminopeptidase / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D010121:Oxytocin / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D010121:Oxytocin; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D002118:Calcium