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Endocrinology Vol. 141, No. 12 4481-4485
Copyright © 2000 by The Endocrine Society


ARTICLES

Oxytocin Stimulates the Translocation of Oxytocinase of Human Vascular Endothelial Cells Via Activation of Oxytocin Receptors1

Hiromi Nakamura, Atsuo Itakuara, Makoto Okamura, Mitsuaki Ito, Akira Iwase, Yutaka Nakanishi, Mayumi Okada, Tetsuro Nagasaka and Shigehiko Mizutani

Maternity and Perinatal Care Center (H.N.) and Division of Pathology, Clinical Laboratory (T.N.), Nagoya University Hospital, Showa-ku, Nagoya 466-8550, Japan; and Department of Obstetrics and Gynecology, Nagoya University School of Medicine (A.I., M.O., M.I., A.I., M.O., S.M.), Showa-ku, Nagoya 466-8550, Japan

Address all correspondence and requests for reprints to: Atsuo Itakura M.D., Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: aita{at}med.nagoya-u.ac.jp

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.




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