Oxytocin stimulates the translocation of oxytocinase of human vascular endothelial cells via activation of oxytocin receptors.
Oxytocinase (OTase) degrades several small peptides such as oxytocin (OT), and thus plays important roles in fetal development and maintenance of human homeostasis during pregnancy. The physiological effects of OT are mediated via its receptor (OTR). Although the interactions between OT and OTR have studied extensively, the relationship to OTase remains to be clarified. It is known that human umbilical vascular endothelial cells express OTR messenger RNA; therefore, they were selected for examination of this question in the present study. RT-PCR experiments confirmed the existence of messenger RNA for OTase, and assessment of protein levels and activity clarified that OT increases the activity of OTase at the cell surface via binding to OTR. This stimulation appears to involve translocation of OTase from cytosolic to the cell surface in response to cellular signal transduction pathways linked to the OTR. Protein kinase C stimulation significantly increased the cell surface activity of OTase, whereas its inhibition resulted in reduction. In summary, our findings provide clear evidence that OT triggers directly OTase translocation in human umbilical vascular endothelial cells via a protein kinase C-dependent pathway coupled to OTR.
Nakamura
H
H
Maternity and Perinatal Care Center, Nagoya University Hospital, Japan.
Itakuara
A
A
Okamura
M
M
Ito
M
M
Iwase
A
A
Nakanishi
Y
Y
Okada
M
M
Nagasaka
T
T
Mizutani
S
S
D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D010122:Cystinyl Aminopeptidase / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018045:Receptors, Oxytocin / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D011493:Protein Kinase C; D010122:Cystinyl Aminopeptidase; D013755:Tetradecanoylphorbol Acetate