Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins. (15th May 2015)

• Record Type: Journal Article
• Authors: Willets, J.M.; Brighton, P.J.; Windell, L.N.; Rana, S.; Nash, C.A.; Konje, J.C.
• Is Part Of: Molecular and cellular endocrinology. Volume 407(2015)
• Page Start: 57
• Page End: 66
• Publication Date: 2015-05-15
• Subjects: Bradykinin -- Myometrium -- Arrestin -- Migration -- Myometrial contraction -- B2 receptor; B2R bradykinin B2 receptor -- [Ca2+]i intracellular calcium concentration -- ERK extracellular signal-regulated kinase -- GPCR G protein-coupled receptor -- GRK G protein-coupled receptor kinase -- eGFP-PH e-GFP-tagged pleckstrin homology domain of phospholipase Cδ -- pERK threonine- and tyrosine-phosphorylated extracellular signal-regulated kinase -- MAPK mitogen-activated protein kinase; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.03.004
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Bradykinin activates Ca 2+ signals via bradykinin B2 receptors in myometrial cells. Arrestin2/3 depletion attenuates bradykinin B2 receptor desensitisation. Arrestin2/3 depletion enhanced bradykinin B2 receptor ERK1/2 signalling. Arrestin3 depletion increased and prolonged bradykinin-stimulated p38 MAPK signals. Bradykinin activates pro-contractile signalling pathways in the human myometrium. Graphical Abstract: Bradykinin-stimulates pro-contractile signalling pathways in human myometrial smooth muscle cells which induces cellular movement. The bradykinin-activated signalling pathways regulated by arrestin proteins are shown alongside potential pathways by which bradykinin may induce a pro-contractile phenotype through MAPK signalling are displayed as '?'. 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 (B2 R) antagonism. Arrestin2 or arrestin3 depletion enhanced and prolonged bradykinin-stimulated Ca 2+ responses, and attenuated B2 R desensitisation. Knockdown of either arrestin enhanced B2 R-stimulated ERK1/2 signals. Moreover, depletion of either arrestin elevated peak-phase p38-MAPK signalling, yet only arrestin3 depletion prolonged B2 R-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.