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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cattaneo, M. G. Chini, B. Vicentini, L. M. |
| Description | Author Affiliation: Cattaneo MG ( Department of Pharmacology, University of Milano, Via Vanvitelli 32, Milano, Italy.) |
| Abstract | BACKGROUND AND PURPOSE: It has recently been reported that oxytocin is produced by some tumour cell types, and that oxytocin receptors, belonging to the G-protein-coupled receptor (GPCR) family, are expressed in a variety of cell types. Among these, human umbilical vein endothelial cells (HUVECs) respond to oxytocin with an increased proliferation, suggesting a possible role for the hormone in the regulation of angiogenesis. EXPERIMENTAL APPROACH: We employed chemotaxis and chemoinvasion assays to characterize the effect of oxytocin on HUVEC motility, and immunoblot analysis to study its molecular mechanisms of action. KEY RESULTS: We showed that oxytocin stimulates migration and invasion in HUVECs via oxytocin receptor activation. Searching for the molecular mechanism(s) responsible for oxytocin's pro-migratory effect, we identified the Gq coupling of oxytocin receptors and phospholipase C (PLC) as the main effectors of oxytocin's action in HUVECs. We also found that oxytocin stimulates the phosphorylation of endothelial nitric oxide synthase (eNOS) via the phosphatidylinositol-3-kinase (PI-3-K)/AKT pathway, and that the activation of PI-3-K and formation of nitric oxide (NO) are required for the pro-migratory effect of oxytocin. CONCLUSIONS AND IMPLICATIONS: The ability of oxytocin to stimulate HUVEC motility and invasion suggests that the hormone can participate in physiopathological processes where activation of endothelial cells plays an important role, for example, in angiogenesis. Interestingly, both the AKT and eNOS phosphorylation induced by oxytocin receptor activation depended on PLC activity, thus suggesting the existence of a still undefined mechanism connecting PLC to the PI-3-K/AKT pathway, upon oxytocin stimulation. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 153 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2008-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Chemotaxis Endothelial Cells Metabolism Oxytocin Receptors, Oxytocin Signal Transduction Cells, Cultured Drug Effects Collagen Dose-Response Relationship, Drug Drug Combinations Enzymology Enzyme Induction GTP-Binding Protein Alpha Subunits, Gq-G11 Laminin Neovascularization, Physiologic Nitric Oxide Nitric Oxide Synthase Type III Analogs & Derivatives Pharmacology Phosphatidylinositol 3-Kinases Phosphorylation Proteoglycans Proto-Oncogene Proteins C-akt Receptor Cross-Talk Receptor, Epidermal Growth Factor Receptors, Vascular Endothelial Growth Factor Type C Phospholipases Vascular Endothelial Growth Factor A Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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