ArticleThe Journal of physiology2000
Inhibition of Rho-associated kinase blocks agonist-induced Ca2+ sensitization of myosin phosphorylation and force in guinea-pig ileum.
Article in The Journal of physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 186 citations in OpenAlex.
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Aging related decreases in NM myosin expression and contractility in a resistance vessel.Frontiers in physiology · 2024Article
- Stretch-Induced Down-Regulation of HCN2 Suppresses Contractile Activity.Molecules (Basel, Switzerland) · 2023Article
- Quantitative real-time measurement of endothelin-1-induced contraction in single non-activated hepatic stellate cells.PloS one · 2021Article
- Inhibition of Rho-kinase improves response to deep inspiration in ovalbumin-sensitized guinea pigs.Iranian journal of basic medical sciences · 2020Article
- Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Inhibition of PI3K promotes dilation of human small airways in a rho kinase-dependent manner.British journal of pharmacology · 2016Article
- Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles.Journal of neurogastroenterology and motility · 2016Review
- Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders.Pharmacological reviews · 2016Review
- Article
- Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2014Article
- Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase.ASN neuro · 2014Article
- The functional significance of the rho/rho-kinase pathway in human erythrocytes.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2014Article
- Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions.Small GTPases · 2014Review
- Lack of transient receptor potential vanilloid 1 channel modulates the development of neurogenic bladder dysfunction induced by cross-sensitization in afferent pathways.Journal of neuroinflammation · 2013Article
- Physiological and pharmacological aspects of the vas deferens-an update.Frontiers in pharmacology · 2013Article
- Rho-ROCK and Rac-PAK signaling pathways have opposing effects on the cell-to-cell spread of Marek's Disease Virus.PloS one · 2012Article
- The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity.The Journal of biological chemistry · 2011Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Ca2+ sensitization of smooth muscle contraction involves the small GTPase RhoA, inhibition of myosin light chain phosphatase (MLCP) and enhanced myosin regulatory light chain (LC20) phosphorylation. A potential effector of RhoA is Rho-associated kinase (ROK). The role of ROK in Ca2+ sensitization was investigated in guinea-pig ileum. Contraction of permeabilized muscle strips induced by GTPgammaS at pCa 6.5 was inhibited by the kinase inhibitors Y-27632, HA1077 and H-7 with IC50 values that correlated with the known Ki values for inhibition of ROK. GTPgammaS also increased LC20 phosphorylation and this was prevented by HA1077. Contraction and LC20 phosphorylation elicited at pCa 5.75 were, however, unaffected by HA1077. Pre-treatment of intact tissue strips with HA1077 abolished the tonic component of carbachol-induced contraction and the sustained elevation of LC20 phosphorylation, but had no effect on the transient or sustained increase in [Ca2+]i induced by carbachol. LC20 phosphorylation and contraction dynamics suggest that the ROK-mediated increase in LC20 phosphorylation is due to MLCP inhibition, not myosin light chain kinase activation. In the absence of Ca2+, GTPgammaS stimulated 35S incorporation from [35S]ATPgammaS into the myosin targeting subunit of MLCP (MYPT). The enhanced thiophosphorylation was inhibited by HA1077. No thiophosphorylation of LC20 was detected. These results indicate that ROK mediates agonist-induced increases in myosin phosphorylation and force by inhibiting MLCP activity through phosphorylation of MYPT. Under Ca2+-free conditions, ROK does not appear to phosphorylate LC20 in situ, in contrast to its ability to phosphorylate myosin in vitro. In particular, ROK activation is essential for the tonic phase of agonist-induced contraction.
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