title: The regulation of myosin phosphatase in pregnant human myometrium.
abstract: Myometrial smooth muscle contractility is regulated predominantly through the reversible phosphorylation of MYLs (myosin light chains), catalysed by MYLK (MYL kinase) and MYLP (MYL phosphatase) activities. MYLK is activated by Ca2+-calmodulin, and most uterotonic agonists operate through myometrial receptors that increase [Ca2+]i (intracellular Ca2+ concentration). Moreover, there is substantial evidence for Ca2+-independent inhibition of MYLP in smooth muscle, leading to generation of increased MYL phosphorylation and force for a given [Ca2+]i, a phenomenon known as 'Ca2+-sensitization'. ROCK (Rho-associated kinase)-mediated phosphorylation and inhibition of MYLP has been proposed as a mechanism for Ca2+-sensitization in smooth muscle. However, it is unclear to date whether the mechanisms that sensitize the contractile machinery to Ca2+ are important in the myometrium, as they appear to be in vascular and respiratory smooth muscle. In the present paper, we discuss the signalling pathways regulating MYLP activity and the involvement of ROCK in myometrial contractility, and present recent data from our laboratory which support a role for Ca2+-sensitization in human myometrium.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (Obstetrics and Gynaecology), School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Hudson
authors.forename: Andrés López
authors.initials: AL
authors.lastname: Bernal
mesh_terms: D020013:Calcium Signaling; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction; D009124:Muscle Proteins; D009215:Myometrium / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010121:Oxytocin / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011247:Pregnancy; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D010121:Oxytocin; D054460:rho-Associated Kinases; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase