title: Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins.
abstract: Bradykinin is associated with infections and inflammation, which given the strong correlation between uterine infection and preterm labour may imply that it could play a role in this process. Therefore, we investigated bradykinin signalling, and the roles that arrestin proteins play in their regulation in human myometrial cells. Bradykinin induced rapid, transient intracellular Ca(2+) increases that were inhibited following B2 receptor (B2R) antagonism. Arrestin2 or arrestin3 depletion enhanced and prolonged bradykinin-stimulated Ca(2+) responses, and attenuated B2R desensitisation. Knockdown of either arrestin enhanced B2R-stimulated ERK1/2 signals. Moreover, depletion of either arrestin elevated peak-phase p38-MAPK signalling, yet only arrestin3 depletion prolonged B2R-induced p38-MAPK signals. Arrestin2-knockdown augmented bradykinin-induced cell movement. Bradykinin stimulates pro-contractile signalling mechanisms in human myometrial cells and arrestin proteins play key roles in their regulation. Our data suggest bradykinin not only acts as an utertonin, but may also have the potential to enhance the contractile environment of the uterus.
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom. Electronic address: jmw23@le.ac.uk.
authors.forename: J M
authors.initials: JM
authors.lastname: Willets
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Brighton
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
authors.forename: L N
authors.initials: LN
authors.lastname: Windell
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Rana
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
authors.forename: C A
authors.initials: CA
authors.lastname: Nash
authors.affiliation: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
authors.forename: J C
authors.initials: JC
authors.lastname: Konje
mesh_terms: D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics*; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002461:Cell Line, Transformed; D002465:Cell Movement; D005260:Female; D054768:G-Protein-Coupled Receptor Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D000071557:beta-Arrestins; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D019390:Arrestins; D034741:RNA, Small Interfering; D043782:Receptor, Bradykinin B2; D000071557:beta-Arrestins; D054768:G-Protein-Coupled Receptor Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D001920:Bradykinin; D002118:Calcium
keywords: Arrestin; B(2) receptor; Bradykinin; Migration; Myometrial contraction; Myometrium