Placental Leucine Aminopeptidase Might Regulate the Effects of Oxytocin with Resolution in Endothelial Cells.
Michiyo Sano, Atsuo Itakura, Mitsuaki Ito, Mikihito Takeuchi, Mayumi Okada, Tomomi Kotani, Shigehiko Mizutani, Fumitaka Kikkawa
Med Sci Monit 2005; 11(7): BR195-199
Background: Oxytocin (OT) is known to cause vascular relaxation via nitricoxide (NO) production and proliferation of endothelial cells. Previously we revealed that human umbilicalvascular endothelial cells (HUVECs) expresses placental leucine aminopeptidase (P-LAP)/insulin regulatedaminopeptidase (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. Material/Methods:Actions of OT on HUVECs transfected with a copy of the human P-LAP gene were therefore examined witha 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 (~3 fold) in P-LAP overexpressing-HUVECsand overexpression of P-LAP resulted in remarkable inhibition of OT effects on HUVECs such as cell proliferation,[Ca(2+)]i, and NO production. Conclusions: These findings suggested that P-LAP on the plasma membranein HUVECs regulates the effects of OT with resolution around OTR.
Keywords: Cystinyl Aminopeptidase - biosynthesis, Cystinyl Aminopeptidase - genetics, Calcium - metabolism, Cell Proliferation - drug effects, Cells, Cultured, Cystinyl Aminopeptidase - genetics, Endothelial Cells - metabolism, Endothelium, Vascular - metabolism, Female, Humans, Nitric Oxide - biosynthesis, Oxytocin - pharmacology, Umbilical Veins - cytology, Vasodilator Agents - pharmacology