Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-10

AUTHORS

M Uehata, T Ishizaki, H Satoh, T Ono, T Kawahara, T Morishita, H Tamakawa, K Yamagami, J Inui, M Maekawa, S Narumiya

ABSTRACT

Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically. Smooth-muscle contraction is regulated by the cytosolic Ca2+ concentration and by the Ca2+ sensitivity of myofilaments: the former activates myosin light-chain kinase and the latter is achieved partly by inhibition of myosin phosphatase. The small GTPase Rho and its target, Rho-associated kinase, participate in this latter mechanism in vitro, but their participation has not been demonstrated in intact muscles. Here we show that a pyridine derivative, Y-27632, selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization. We identified the Y-27632 target as a Rho-associated protein kinase, p160ROCK. Y-27632 consistently suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells and dramatically corrects hypertension in several hypertensive rat models. Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically. More... »

PAGES

990-994

References to SciGraph publications

Journal

TITLE

Nature

ISSUE

6654

VOLUME

389

Related Patents

  • Methods For Treating A Disease In Which Rho Kinase Is Involved
  • Methods For Treating A Disease In Which Rho Kinase Is Involved
  • Preventives/Remedies For Glaucoma
  • Agent For Prophylaxis And Treatment Of Glaucoma
  • High-Throughput Screening Method
  • Cycloalkylamine Substituted Isoquinoline And Isoquinolinone Derivatives
  • Inhibitors Of Influenza Viruses Replication
  • Isoquinoline Derivatives
  • Inhibitors Of Influenza Viruses Replication
  • 6-Substituted Isoquinolines And Isoquinolinones
  • Indazole Derivatives
  • Chimeric Peptides For The Regulation Of Gtpases
  • Cyclohexylamin Isoquinolone Derivatives
  • Isoquinoline Derivatives
  • 6-Aminoimidazo[1,2-B]Pyridazine Analogs As Rho Kinase Inhibitors For The Treatment Of Rho Kinase-Mediated Diseases And Conditions
  • Inhibitors Of Influenza Viruses Replication
  • Rho Kinase Inhibitors And Methods Of Use
  • Substituted Isoquinoline And Isoquinolinone Derivatives
  • Chimeric Peptides For The Regulation Of Gtpases
  • Piperidinyl-Substituted Isoquinolone Derivatives
  • Cycloalkylamine Substituted Isoquinolone Derivatives
  • Fasudil In Combination Therapies For The Treatment Of Pulmonary Arterial Hypertension
  • Bi- And Polycyclic Substituted Isoquinoline And Isoquinolinone Derivatives
  • Hetaryloxy-Substituted Phenylamino Pyrimidines As Rho Kinase Inhibitors
  • In Vitro Differentiation Of Pluripotent Stem Cells To Pancreatic Endoderm Cells (Pec) And Endocrine Cells
  • 4-(4-Pyridinyl)-Benzamides And Their Use As Rock Activity Modulators
  • Pyridylthiazole-Based Ureas As Inhibitors Of Rho Associated Protein Kinase (Rock) And Methods Of Use
  • Inhibitors Of Influenza Viruses Replication
  • Preventives/Remedies For Glaucoma
  • Cycloalkylamine Substituted Isoquinoline Derivatives
  • Inhibitors Of Influenza Viruses Replication
  • T Cell Activation Inhibitor, Pharmaceutical Composition Containing Same, And Screening Method For T Cell Activation Inhibiting Substance
  • 4-(4-Pyridinyl)-Benzamides And Their Use As Rock Activity Modulators
  • Substituted Isoquinoline And Isoquinolinone Derivatives
  • Substituted Isoquinoline And Isoquinolinone Derivatives
  • Inhibitors Of Influenza Viruses Replication
  • High-Throughput Screening Method
  • Inhibitors Of Influenza Viruses Replication
  • Chimeric Peptides For The Regulation Of Gtpases
  • Methods Of Preparing Inhibitors Of Influenza Viruses Replication
  • (Indazol-5-Yl)-Pyrazines And (1,3-Dihydro-Indol-2-One)-Pyrazines For Treating Glaucoma And Controlling Intraocular Pressure
  • Substituted Isoquinoline And Isoquinolinone Derivatives As Inhibitors Of Rho-Kinase
  • Method For Generating Pancreatic Hormone-Producing Cells
  • Method Of Diagnosing And Treating Interstitial Cystitis
  • Substituted Isoquinolines And Isoquinolinones As Rho Kinase Inhibitors
  • Rho Kinase Inhibitors
  • Cell Culture Platform For Single Cell Sorting And Enhanced Reprogramming Of Ipscs
  • Inhibitors Of Influenza Viruses Replication
  • Cyclohexylamine Isoquinolone Derivatives
  • Inhibitors Of Influenza Viruses Replication
  • Fasudil In Combination Therapies For The Treatment Of Pulmonary Arterial Hypertension
  • Hydroxyamino- And Amino-Substituted Pyridine Analogs For Treating Rho Kinase-Mediated Diseases And Conditions
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/40187

    DOI

    http://dx.doi.org/10.1038/40187

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1014459412

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9353125


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1116", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical Physiology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amides", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antihypertensive Agents", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "COS Cells", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Calcium", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Adhesion", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Enzyme Inhibitors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Guinea Pigs", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hypertension", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "In Vitro Techniques", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Intracellular Signaling Peptides and Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Muscle Contraction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Muscle, Smooth, Vascular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein-Serine-Threonine Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Pyridines", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Rabbits", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Radioligand Assay", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Rats", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Rats, Wistar", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Swine", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "rho-Associated Kinases", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Mitsubishi Chemical Holdings (Japan)", 
              "id": "https://www.grid.ac/institutes/grid.418306.8", 
              "name": [
                "Discovery Research (Tokyo), Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan. uehata@yoshitomi.co.jp"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Uehata", 
            "givenName": "M", 
            "id": "sg:person.0753613500.30", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753613500.30"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Ishizaki", 
            "givenName": "T", 
            "id": "sg:person.0745315472.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0745315472.00"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Satoh", 
            "givenName": "H", 
            "type": "Person"
          }, 
          {
            "familyName": "Ono", 
            "givenName": "T", 
            "type": "Person"
          }, 
          {
            "familyName": "Kawahara", 
            "givenName": "T", 
            "type": "Person"
          }, 
          {
            "familyName": "Morishita", 
            "givenName": "T", 
            "id": "sg:person.0775526242.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775526242.47"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Tamakawa", 
            "givenName": "H", 
            "type": "Person"
          }, 
          {
            "familyName": "Yamagami", 
            "givenName": "K", 
            "type": "Person"
          }, 
          {
            "familyName": "Inui", 
            "givenName": "J", 
            "type": "Person"
          }, 
          {
            "familyName": "Maekawa", 
            "givenName": "M", 
            "id": "sg:person.01131250716.79", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01131250716.79"
            ], 
            "type": "Person"
          }, 
          {
            "familyName": "Narumiya", 
            "givenName": "S", 
            "id": "sg:person.01122725670.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01122725670.71"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1016/s0955-0674(97)80156-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001293675"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.16.10.5313", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001458793"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0006-291x(89)92189-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003002962"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.93.3.1340", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005879203"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0014-2999(84)90468-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005955638"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0014-2999(84)90468-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005955638"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0076-6879(74)38047-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006930750"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0014-5793(96)00811-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006943299"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/372231a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007748676", 
              "https://doi.org/10.1038/372231a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.270.39.22731", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017452790"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/367040a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021411105", 
              "https://doi.org/10.1038/367040a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.275.5304.1308", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023493290"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0076-6879(82)85029-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024401042"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(92)90163-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024551498"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0014-5793(97)00107-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026602734"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.88.20.9307", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031562048"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.270.49.29051", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033511926"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0092-8674(92)90164-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040198227"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi00316a032", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055169899"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/oxfordjournals.jbchem.a021401", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1059960203"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.273.5272.245", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062553597"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1986.65.1.0080", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071094381"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1986.65.1.0080", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071094381"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1986.65.1.0080", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071094381"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1077025146", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078929282", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078951573", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079559244", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082173616", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1996.tb00539.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1082881257"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1996.tb00574.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1082890075"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1997-10", 
        "datePublishedReg": "1997-10-01", 
        "description": "Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically. Smooth-muscle contraction is regulated by the cytosolic Ca2+ concentration and by the Ca2+ sensitivity of myofilaments: the former activates myosin light-chain kinase and the latter is achieved partly by inhibition of myosin phosphatase. The small GTPase Rho and its target, Rho-associated kinase, participate in this latter mechanism in vitro, but their participation has not been demonstrated in intact muscles. Here we show that a pyridine derivative, Y-27632, selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization. We identified the Y-27632 target as a Rho-associated protein kinase, p160ROCK. Y-27632 consistently suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells and dramatically corrects hypertension in several hypertensive rat models. Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/40187", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0090-0028", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6654", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "389"
          }
        ], 
        "name": "Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension", 
        "pagination": "990-994", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "44e2cb25843dd1ab7081e0c850a4f6441b801d8093c58a2c32256852e266e176"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "9353125"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0410462"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/40187"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1014459412"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/40187", 
          "https://app.dimensions.ai/details/publication/pub.1014459412"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T12:15", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000361_0000000361/records_54014_00000000.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/nature/journal/v389/n6654/full/389990a0.html"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/40187'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/40187'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/40187'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/40187'


     

    This table displays all metadata directly associated to this object as RDF triples.

    300 TRIPLES      21 PREDICATES      81 URIs      45 LITERALS      33 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/40187 schema:about N0c50a457b7ac4419b3dd0c4ff9ae4162
    2 N0e8c969b40254d9c89fc577767a6ede5
    3 N122d68078dbc4d1cbd16d4baa2ed9d6a
    4 N123ff632050142d9a03e48e7361ea69a
    5 N408f9e85131944e7a53eb41161d3c919
    6 N6629c111758942eca4b12275510efae3
    7 N71f5141a406e46bc85e3ef3f65d85e20
    8 N765fe4d2f125490b81a63ba1389f73de
    9 N7d8866a07c834249abb796f276715b7a
    10 N84d9408b9d0d4db88f25d276978209a1
    11 N88a5ffabf648476eb547283610cfeddb
    12 N8f6f459bc7a64adda593d6a56df4a455
    13 Na406198ec518403fbc2a684290fec757
    14 Na69cfaa333b84a4da8bc77abcfbd9c2c
    15 Nb5ee8e7bec15413fae04c167e5fa9983
    16 Nc3a70a90aebd4040a1c49dd05733e65f
    17 Nc6d3ce8ee4a8403ea331ca2e8df51146
    18 Nc6e3f8be2dd7446a917a17374b3a6c3c
    19 Ncb77a99543c14371b5976d37bd68218d
    20 Ne7b8f41c93bf4d419e13d950c970802f
    21 Nf114df68f9334562a456901d1448e3d3
    22 Nf9e5bf5b98ba44aa8472a7d88688fabc
    23 Nfd641b197cbd4865b1a5e4d763c2b264
    24 Nfff3e216ff55458db33ba903f70fb11a
    25 anzsrc-for:11
    26 anzsrc-for:1116
    27 schema:author Na0d5c2a97949499f97f94b6f04b566f8
    28 schema:citation sg:pub.10.1038/367040a0
    29 sg:pub.10.1038/372231a0
    30 https://app.dimensions.ai/details/publication/pub.1077025146
    31 https://app.dimensions.ai/details/publication/pub.1078929282
    32 https://app.dimensions.ai/details/publication/pub.1078951573
    33 https://app.dimensions.ai/details/publication/pub.1079559244
    34 https://app.dimensions.ai/details/publication/pub.1082173616
    35 https://doi.org/10.1002/j.1460-2075.1996.tb00539.x
    36 https://doi.org/10.1002/j.1460-2075.1996.tb00574.x
    37 https://doi.org/10.1016/0006-291x(89)92189-x
    38 https://doi.org/10.1016/0014-2999(84)90468-0
    39 https://doi.org/10.1016/0014-5793(96)00811-3
    40 https://doi.org/10.1016/0076-6879(74)38047-0
    41 https://doi.org/10.1016/0076-6879(82)85029-5
    42 https://doi.org/10.1016/0092-8674(92)90163-7
    43 https://doi.org/10.1016/0092-8674(92)90164-8
    44 https://doi.org/10.1016/s0014-5793(97)00107-5
    45 https://doi.org/10.1016/s0955-0674(97)80156-1
    46 https://doi.org/10.1021/bi00316a032
    47 https://doi.org/10.1073/pnas.88.20.9307
    48 https://doi.org/10.1073/pnas.93.3.1340
    49 https://doi.org/10.1074/jbc.270.39.22731
    50 https://doi.org/10.1074/jbc.270.49.29051
    51 https://doi.org/10.1093/oxfordjournals.jbchem.a021401
    52 https://doi.org/10.1126/science.273.5272.245
    53 https://doi.org/10.1126/science.275.5304.1308
    54 https://doi.org/10.1128/mcb.16.10.5313
    55 https://doi.org/10.3171/jns.1986.65.1.0080
    56 schema:datePublished 1997-10
    57 schema:datePublishedReg 1997-10-01
    58 schema:description Abnormal smooth-muscle contractility may be a major cause of disease states such as hypertension, and a smooth-muscle relaxant that modulates this process would be useful therapeutically. Smooth-muscle contraction is regulated by the cytosolic Ca2+ concentration and by the Ca2+ sensitivity of myofilaments: the former activates myosin light-chain kinase and the latter is achieved partly by inhibition of myosin phosphatase. The small GTPase Rho and its target, Rho-associated kinase, participate in this latter mechanism in vitro, but their participation has not been demonstrated in intact muscles. Here we show that a pyridine derivative, Y-27632, selectively inhibits smooth-muscle contraction by inhibiting Ca2+ sensitization. We identified the Y-27632 target as a Rho-associated protein kinase, p160ROCK. Y-27632 consistently suppresses Rho-induced, p160ROCK-mediated formation of stress fibres in cultured cells and dramatically corrects hypertension in several hypertensive rat models. Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically.
    59 schema:genre research_article
    60 schema:inLanguage en
    61 schema:isAccessibleForFree false
    62 schema:isPartOf N9670de5d07184691a44b088782a2a2e0
    63 Ne71686744bdc49a58c23d7c1f7b56cdf
    64 sg:journal.1018957
    65 schema:name Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    66 schema:pagination 990-994
    67 schema:productId N21bf01d2209c4d0299954cdce679bdd3
    68 N3e2c8615466745ebb133eff4e5f275be
    69 N58210aaab4284a619b375d67f5f06f51
    70 N7f3ddf51da7b4185a6342def30ee838e
    71 Ne8076af071244242b87caf25406ef0b1
    72 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014459412
    73 https://doi.org/10.1038/40187
    74 schema:sdDatePublished 2019-04-11T12:15
    75 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    76 schema:sdPublisher N4d73b69f859f43d1888718ec0c442a10
    77 schema:url http://www.nature.com/nature/journal/v389/n6654/full/389990a0.html
    78 sgo:license sg:explorer/license/
    79 sgo:sdDataset articles
    80 rdf:type schema:ScholarlyArticle
    81 N0c50a457b7ac4419b3dd0c4ff9ae4162 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    82 schema:name Calcium
    83 rdf:type schema:DefinedTerm
    84 N0e8c969b40254d9c89fc577767a6ede5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    85 schema:name Cell Adhesion
    86 rdf:type schema:DefinedTerm
    87 N122d68078dbc4d1cbd16d4baa2ed9d6a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    88 schema:name Hypertension
    89 rdf:type schema:DefinedTerm
    90 N123ff632050142d9a03e48e7361ea69a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    91 schema:name In Vitro Techniques
    92 rdf:type schema:DefinedTerm
    93 N21bf01d2209c4d0299954cdce679bdd3 schema:name pubmed_id
    94 schema:value 9353125
    95 rdf:type schema:PropertyValue
    96 N2749cab35ea44547a8e9860e4e22a6d2 rdf:first N3b473ce8f51940548f79e2fe7e2fbc2e
    97 rdf:rest Nd79a9feac64e4473ab9607ba463ec4d9
    98 N32d6e2f0f41443a796245d69e80a8f20 schema:familyName Inui
    99 schema:givenName J
    100 rdf:type schema:Person
    101 N36bbacc1e9434e598b6bc6c32119f25a schema:familyName Tamakawa
    102 schema:givenName H
    103 rdf:type schema:Person
    104 N3b473ce8f51940548f79e2fe7e2fbc2e schema:familyName Yamagami
    105 schema:givenName K
    106 rdf:type schema:Person
    107 N3e2c8615466745ebb133eff4e5f275be schema:name nlm_unique_id
    108 schema:value 0410462
    109 rdf:type schema:PropertyValue
    110 N3fe770034a6c4f6cb22c5b73116c51de rdf:first Nbe692a23868f474e8147da1ec05a7ebf
    111 rdf:rest Ne82bc4c3b956470290fe16ab4aab0233
    112 N408f9e85131944e7a53eb41161d3c919 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    113 schema:name Recombinant Proteins
    114 rdf:type schema:DefinedTerm
    115 N4d73b69f859f43d1888718ec0c442a10 schema:name Springer Nature - SN SciGraph project
    116 rdf:type schema:Organization
    117 N58210aaab4284a619b375d67f5f06f51 schema:name doi
    118 schema:value 10.1038/40187
    119 rdf:type schema:PropertyValue
    120 N6629c111758942eca4b12275510efae3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    121 schema:name Animals
    122 rdf:type schema:DefinedTerm
    123 N66db4521662245fabc6d0681d1725151 rdf:first sg:person.01122725670.71
    124 rdf:rest rdf:nil
    125 N6977bcf1a20e45028f541ee01deb6e35 rdf:first Nd76ccac37c2d43d4b8db26927ded97d8
    126 rdf:rest N3fe770034a6c4f6cb22c5b73116c51de
    127 N71f5141a406e46bc85e3ef3f65d85e20 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    128 schema:name Male
    129 rdf:type schema:DefinedTerm
    130 N765fe4d2f125490b81a63ba1389f73de schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Amides
    132 rdf:type schema:DefinedTerm
    133 N7d8866a07c834249abb796f276715b7a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Muscle Contraction
    135 rdf:type schema:DefinedTerm
    136 N7f3ddf51da7b4185a6342def30ee838e schema:name readcube_id
    137 schema:value 44e2cb25843dd1ab7081e0c850a4f6441b801d8093c58a2c32256852e266e176
    138 rdf:type schema:PropertyValue
    139 N84d9408b9d0d4db88f25d276978209a1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    140 schema:name Radioligand Assay
    141 rdf:type schema:DefinedTerm
    142 N88a5ffabf648476eb547283610cfeddb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Antihypertensive Agents
    144 rdf:type schema:DefinedTerm
    145 N8f6f459bc7a64adda593d6a56df4a455 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name COS Cells
    147 rdf:type schema:DefinedTerm
    148 N9369be4920944de0b988291ecd7a3399 rdf:first sg:person.01131250716.79
    149 rdf:rest N66db4521662245fabc6d0681d1725151
    150 N9670de5d07184691a44b088782a2a2e0 schema:volumeNumber 389
    151 rdf:type schema:PublicationVolume
    152 Na0d5c2a97949499f97f94b6f04b566f8 rdf:first sg:person.0753613500.30
    153 rdf:rest Na6e423256bef454ca817d6bc6c497c66
    154 Na406198ec518403fbc2a684290fec757 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Intracellular Signaling Peptides and Proteins
    156 rdf:type schema:DefinedTerm
    157 Na69cfaa333b84a4da8bc77abcfbd9c2c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Protein-Serine-Threonine Kinases
    159 rdf:type schema:DefinedTerm
    160 Na6e423256bef454ca817d6bc6c497c66 rdf:first sg:person.0745315472.00
    161 rdf:rest Nbe6383c82f7b4d6f92f7a8442b595c44
    162 Nb5ee8e7bec15413fae04c167e5fa9983 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Guinea Pigs
    164 rdf:type schema:DefinedTerm
    165 Nbe6383c82f7b4d6f92f7a8442b595c44 rdf:first Nc136978d855f4409b8c092f25c89d77f
    166 rdf:rest N6977bcf1a20e45028f541ee01deb6e35
    167 Nbe692a23868f474e8147da1ec05a7ebf schema:familyName Kawahara
    168 schema:givenName T
    169 rdf:type schema:Person
    170 Nc136978d855f4409b8c092f25c89d77f schema:familyName Satoh
    171 schema:givenName H
    172 rdf:type schema:Person
    173 Nc3a70a90aebd4040a1c49dd05733e65f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Swine
    175 rdf:type schema:DefinedTerm
    176 Nc6d3ce8ee4a8403ea331ca2e8df51146 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Muscle, Smooth, Vascular
    178 rdf:type schema:DefinedTerm
    179 Nc6e3f8be2dd7446a917a17374b3a6c3c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    180 schema:name Rats, Wistar
    181 rdf:type schema:DefinedTerm
    182 Ncb77a99543c14371b5976d37bd68218d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name Enzyme Inhibitors
    184 rdf:type schema:DefinedTerm
    185 Nd76ccac37c2d43d4b8db26927ded97d8 schema:familyName Ono
    186 schema:givenName T
    187 rdf:type schema:Person
    188 Nd79a9feac64e4473ab9607ba463ec4d9 rdf:first N32d6e2f0f41443a796245d69e80a8f20
    189 rdf:rest N9369be4920944de0b988291ecd7a3399
    190 Ne369460c9f5546c098f5e8e713bd479c rdf:first N36bbacc1e9434e598b6bc6c32119f25a
    191 rdf:rest N2749cab35ea44547a8e9860e4e22a6d2
    192 Ne71686744bdc49a58c23d7c1f7b56cdf schema:issueNumber 6654
    193 rdf:type schema:PublicationIssue
    194 Ne7b8f41c93bf4d419e13d950c970802f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    195 schema:name rho-Associated Kinases
    196 rdf:type schema:DefinedTerm
    197 Ne8076af071244242b87caf25406ef0b1 schema:name dimensions_id
    198 schema:value pub.1014459412
    199 rdf:type schema:PropertyValue
    200 Ne82bc4c3b956470290fe16ab4aab0233 rdf:first sg:person.0775526242.47
    201 rdf:rest Ne369460c9f5546c098f5e8e713bd479c
    202 Nf114df68f9334562a456901d1448e3d3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    203 schema:name Humans
    204 rdf:type schema:DefinedTerm
    205 Nf9e5bf5b98ba44aa8472a7d88688fabc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    206 schema:name Rabbits
    207 rdf:type schema:DefinedTerm
    208 Nfd641b197cbd4865b1a5e4d763c2b264 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    209 schema:name Pyridines
    210 rdf:type schema:DefinedTerm
    211 Nfff3e216ff55458db33ba903f70fb11a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    212 schema:name Rats
    213 rdf:type schema:DefinedTerm
    214 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    215 schema:name Medical and Health Sciences
    216 rdf:type schema:DefinedTerm
    217 anzsrc-for:1116 schema:inDefinedTermSet anzsrc-for:
    218 schema:name Medical Physiology
    219 rdf:type schema:DefinedTerm
    220 sg:journal.1018957 schema:issn 0090-0028
    221 1476-4687
    222 schema:name Nature
    223 rdf:type schema:Periodical
    224 sg:person.01122725670.71 schema:familyName Narumiya
    225 schema:givenName S
    226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01122725670.71
    227 rdf:type schema:Person
    228 sg:person.01131250716.79 schema:familyName Maekawa
    229 schema:givenName M
    230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01131250716.79
    231 rdf:type schema:Person
    232 sg:person.0745315472.00 schema:familyName Ishizaki
    233 schema:givenName T
    234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0745315472.00
    235 rdf:type schema:Person
    236 sg:person.0753613500.30 schema:affiliation https://www.grid.ac/institutes/grid.418306.8
    237 schema:familyName Uehata
    238 schema:givenName M
    239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0753613500.30
    240 rdf:type schema:Person
    241 sg:person.0775526242.47 schema:familyName Morishita
    242 schema:givenName T
    243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775526242.47
    244 rdf:type schema:Person
    245 sg:pub.10.1038/367040a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021411105
    246 https://doi.org/10.1038/367040a0
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1038/372231a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007748676
    249 https://doi.org/10.1038/372231a0
    250 rdf:type schema:CreativeWork
    251 https://app.dimensions.ai/details/publication/pub.1077025146 schema:CreativeWork
    252 https://app.dimensions.ai/details/publication/pub.1078929282 schema:CreativeWork
    253 https://app.dimensions.ai/details/publication/pub.1078951573 schema:CreativeWork
    254 https://app.dimensions.ai/details/publication/pub.1079559244 schema:CreativeWork
    255 https://app.dimensions.ai/details/publication/pub.1082173616 schema:CreativeWork
    256 https://doi.org/10.1002/j.1460-2075.1996.tb00539.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1082881257
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1002/j.1460-2075.1996.tb00574.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1082890075
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1016/0006-291x(89)92189-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1003002962
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1016/0014-2999(84)90468-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005955638
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1016/0014-5793(96)00811-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006943299
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/0076-6879(74)38047-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006930750
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1016/0076-6879(82)85029-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024401042
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1016/0092-8674(92)90163-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024551498
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1016/0092-8674(92)90164-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040198227
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1016/s0014-5793(97)00107-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026602734
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1016/s0955-0674(97)80156-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001293675
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1021/bi00316a032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055169899
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1073/pnas.88.20.9307 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031562048
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1073/pnas.93.3.1340 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005879203
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1074/jbc.270.39.22731 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017452790
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1074/jbc.270.49.29051 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033511926
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1093/oxfordjournals.jbchem.a021401 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059960203
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1126/science.273.5272.245 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062553597
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1126/science.275.5304.1308 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023493290
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1128/mcb.16.10.5313 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001458793
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.3171/jns.1986.65.1.0080 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071094381
    297 rdf:type schema:CreativeWork
    298 https://www.grid.ac/institutes/grid.418306.8 schema:alternateName Mitsubishi Chemical Holdings (Japan)
    299 schema:name Discovery Research (Tokyo), Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan. uehata@yoshitomi.co.jp
    300 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...