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Uncoupling of force and myosin light chain phosphorylation produced by slow stretch in vascular smooth muscle.

Research Project

Project/Area Number 10670093
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka

Principal Investigator

OBARA Kazuo  Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, 薬学部, 講師 (60117611)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsdog / vascular smooth muscle / basilar artery / stretch stimulation / myosin phosphorylation / protein kinase C / myosin phosphatase / Rho / 収縮
Research Abstract

Relationship between force and myosin light chain (MLC) phosphorylation in slow stretch-induced contraction in canine basilar artery was investigated. In the presence of tetraethyl-ammonium (5 mM), slow stretch at a rate of 1 mm/sec up to 1.5 times initial muscle length during a stimulus period of 15 min produced an increase in multiple phosphorylated MLC species (at least mono-, di- and tri-phosphorylated species) without any apparent contraction, indicating uncoupling of force and MLC phosphorylation. Slow stretch also increased translocation of protein kinase C (PKC)-α and PKC-δ from the cytosol to the membrane fraction. The MLC phosphorylation was inhibited by nicardipine (a 1,4-dihydropyridine Ca^<2+> channel blocker), ML-9 (an inhibitor of myosin light chain kinase) or calphostin C (a cPKC/nPKC inhibitor) to about 50% of that in drug-untreated artery. Y-27632 ( a Rho-kinase inhibitor) abolished the MLC phosphorylation. In contrast, rottlerin (5 μM, a putative inhibitor of PKC-δ) had no apparent effect on MLC phosphorylation. The translocation of PKC-α was inhibited by only calphostin C, and that of PKC-δ was attenuated by calphostin C, Y-27632 or rottlerin. Okadaic acid (an inhibitor of phosphatase) inhibited 80 mM KCl-induced contraction, but it increased multiple phosphorylated MLC species.
Considering that the translocation of PKC-α and δ is important for their activation, the present results suggest that Rho/Rho-kinase activity and PKC other than PKC-δ are involved in MLC phosphorylation without contraction.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] K.Obara,M.Saito,A.Yamanaka,M.Uchino and K.Nakayama: "Involvement of different activator Ca^<2+> in the rate-dependent stretch-induced contractions of canine basilar artery."Japanese Journal of Physiology. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Nob,H.Nobe,K.Obara,R.J.Paul: "Preferential role of intracellular Ca^<2+> stores in regulation of isometric force in NIH 3T3 fibroblast fibers."Journal of Physiology. 529. 669-679 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Obara,M.Koide,T.Ishikawa,Y.Tanabe,K.Nakayama: "Protein kinase Cδ but not PKCε activity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery."Journal of Cardiovascular Pharmacology. 36(Supl 1). 120-121 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Saitou,T.Ishikawa,K.Obara,K.Nakayama K: "Characterization of whole-cell currents elicited by mechanical stimulation of Xenopus oocytes"Pflugers Archiv : European Journal of Physiology. 440. 858-865 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Obara,K.Nobe,H.Nobe,M.S.Kolodncy,P.de Lanerollc,R.J.Paul: "Effects of microtubules and microfilaments on [Ca^<2+>]_i and contractility in a reconstituted fibroblast fiber."American Journal of Physiology. 279. C785-C796 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kimura,T.Sasase,T.Ishikawa,Y.Tanabe,K.Nakayama: "Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes."British Journal of Pharmacology. 130. 923-931 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Nishizawa,K.Obara,K.Nakayama,M.Koide,T.Yokoyama,N.Yokota,S.Ohta: "Protein kinase Cδ and α are involved in the development of vasospasm after subarachnoid hemorrhage."European Journal of Pharmacology. 398. 113-119 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 小原一男,小出昌代,石川智久,田辺由幸,中山貢一: "メカノセンサー機構の実体と機能-新しい視点からの創薬への展望-:5.イヌ脳底動脈における張力発生を伴わない伸展誘発性ミオシン軽鎖のリン酸化について"日本薬理学雑誌. 116. 354-355 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Obara,S.Hata,K.Sato,M.Koide,K.Isjii,K.Nakayama: "Contractile potentiation by endothelin-1 involves protein kinase C-δ activity in porcine coronary artery."Japanese Journal of Physiology. 49. 175-183 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 増本直広,中山貢一,小原一男,田辺由幸: "特集 脳循環の調節;脳血管のmyogenic response."血管と内皮. 8. 349-356 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuo Obara, Michihiro Saito, Akihiro Yamanaka, Mayumi Uchino and Koichi Nakayama: "Involvement of different activator Ca^<2+> in the rate-dependent stretch-induced contractions of canine basilar artery."Jpn.J.Physiol.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koji Nobe, Hiromi Nobe, Kazuo Obara, Richard J.Paul: "Preferential role of intracellular Ca^<2+> stores in regulation of isometric force in NIH 3T3 fibroblast fibres."J.Physiol.(Lond.).. 529. 669-679 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Obara, K, Nobe, K, Nobe, H, Kolodney, MS, de Lanerolle, P and Paul, RJ: "Effects of microtubules and microfilaments on [Ca^<2+>]_i and contractility in a reconstituted fibroblast fiber."Am.J.Physiol.. 279. C785-C796 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuo Obara, Masayo Koide, Tomohisa Ishikawa, Yoshiyuki Tanabe and Koichi Nakayama: "Protein kinase Cδ but not PKCε activity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery."J.Cardiovas.Pharmacol.. 36 (Supl.1). S120-S121 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Saito, T.Ishikawa, K.Obara and K.Nakayama: "Characterization of whole-cell currents elicited by mechanical stimulation of Xenopus oocytes."Pflugers Arch.. 440. 858-865 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Makoto Kimura, Kazuo Obara, Tomohiko Sasase, Tomohisa Ishikawa, Yoshiyuki Tanabe and Koichi Nakayama: "Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes."Br.J.Pharmaco.. 130. 923-931 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeru Nishizawa, Kazuo Obara, Koichi Nakayama, Masayo Koide, Tetsuo Yokoyama, Naoki Yokota and Seiji Ohta: "Protein kinase Cδ and α are involved in the development of vasospasm after subarachnoid hemorrhage."Eur.J.Pharmacol.. 398. 113-119 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuo Obara, Shinzo Hata, Katsura Sato, Masayo Koide, Kunio Ishii and Koichi Nakayama: "Contractile potentiation by endothelin-1 involves protein kinase C-δ activity in porcine coronary artery."Jpn.J.Physiol.. 49. 175-183 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Obara,M.Saito,A.Yamanaka,M.Uchino and K.Nakayama: "Involvement of different activator Ca^<2+> in the rate-dependent stretch-induced contractions of canine basilar artery."Japanese Journal of Physiology. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Nob,H.Nobe,K.Obara,R.J.Paul: "Preferential role of intracellular Ca^<2+> stores in regulation of isometric force in NIH 3T3 fibroblast fibers."Journal of Physiology. 529. 669-679 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Obara,M.Koide,T.Ishikawa,Y.Tanabe,K.Nakayama: "Protein kinase Cδ but not PKCεactivity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery."Journal of Cardiovascular Pharmacology. 36(Supl 1). 120-121 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Saitou,T.Ishikawa,K.Obara,K.Nakayama K: "Characterization of whole-cell currents elicited by mechanical stimulation of Xenopus oocytes."Pflugers Archiv : European Journal of Physiology. 440. 858-865 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Obara,K.Nobe,H.Nobe,M.S.Kolodney,P.de Lanerolle,R.J.Paul: "Effects of microtubules and microfilaments on [Ca^<2+>]_i and contractility in a reconstituted fibroblast fiber."American Journal of Physiology. 279. C785-C796 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kimura,T.Sasase,T.Ishikawa,Y.Tanabe,K.Nakayama: "Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes."British Journal of Pharmacology. 130. 923-931 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Nishizawa,K.Obara,K.Nakayama,M.Koide,T.Yokoyama,N.Yokota,S.Ohta: "Protein kinase Cδ and α are involved in the development of vasospasm after subarachnoid hemorrhage."European Journal of Pharmacology. 398. 113-119 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小原一男,小出昌代,石川智久,田辺由幸,中山貢一: "メカノセンサー機構の実体と機能-新しい視点からの創薬への展望-:5.イヌ脳底動脈における張力発生を伴わない伸展誘発性ミオシン軽鎖のリン酸化について"日本薬理学雑誌. 116. 354-355 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Obara,M.Koide,T.Ishikawa,Y.Tanabe,K.Nakayama: "Protein kinase Cδ but not PKCε activity is involved in contractile potentiation by endothelin-1in the porcine coronary artery"Journal of Cardiovascular Pharmacology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Obara,S.Hata,K.Sato,M.Koide,K.Ishii,K.Nakayama: "Contractile potentiation by endothelin-1 involves protein kinase C-δ activity in porcine coronary artery"Japanese Journal of Physiology. 49. 175-183 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 増本直広、中山貢一、小原一男、田辺由幸: "脳血管のmyogenic response"血管と内皮. 8(4). 349-356 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Obara,M.Uchino,M.Koide,K.Nakayama: "Uncoupling of force and myosin light chain phosphorylation produced by slow stretch involves Rho activity in canine basilar artery"Biophysical Journal. 74(2). A258 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 増本直広: "脳血管のmyogenic response" 血管と内皮. 8(4). 349-356 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazuo OBARA: "Uncoupling of force and myosin light chain phosphorylation produced by slow stretch involves Rho activity in canine basilar artery." Biophysical Journal. 74(2). A258 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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