Placental leucine aminopeptidase might regulate the effects of oxytocin with resolution in endothelial cells

Med Sci Monit. 2005 Jul;11(7):BR195-9. Epub 2005 Jun 29.

Abstract

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.

Material/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cystinyl Aminopeptidase / biosynthesis*
  • Cystinyl Aminopeptidase / genetics
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Nitric Oxide / biosynthesis
  • Oxytocin / pharmacology*
  • Umbilical Veins / cytology
  • Vasodilator Agents / pharmacology*

Substances

  • Vasodilator Agents
  • Nitric Oxide
  • Oxytocin
  • Cystinyl Aminopeptidase
  • leucyl-cystinyl aminopeptidase
  • Calcium