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Intracellular signal transduction of parathyroid hormone receptor activation and its pathphysiology

Research Project

Project/Area Number 07456129
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionHokkaido University

Principal Investigator

ITO Shigeo  Hokkaido Univ., Graduate School. of Vet.Med., Associate Professor, 大学院・獣医学研究科, 助教授 (40109509)

Co-Investigator(Kenkyū-buntansha) OHTA Toshio  Hokkaido Univ., Graduate School of Vet.Med., Lecturer, 大学院・獣医学研究科, 講師 (20176895)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordsdog parathyroid hormone / PTH receptors / cDNA cloning / northern blot analysis / cyclic AMP / smooth muscles / intracellular Ca^<2+> concentration / whole-cell voltage clamp / ノーザンプロット解析 / パラサイロイドホルモン / 血管平滑筋 / 細胞内情報伝達
Research Abstract

1. In order to deduce the amino acid sequence of dog parathyroid hormone (PTH) receptors, cDNA cloning was carried out using the cDNA library of the liver and kidney. We found that dog PTH receptors were putative G protein-coupled membrane protein having seven membrane spanning domains and that the amino acid sequence of PTH receptors of the dog was homologus that of human (95.3%), rat (88.0%) or opossum (79.1%). The northern blot analysis showed that PTH receptors were expressed in the kidney, liver, brain, aorta and bone marrow. 2. The effect of PTH on contractions and changes in intracellular Ca^<2+> ( [Ca^<2+>] in) was examined in the rat superior mesenteric artery to know the intracellular signal transduction of the PTH receptor activation. PTH inhibited a contraction and increase in [Ca^<2+>] in induced by phenyrephrine greater than that by high concentrations of KCI (high K). PTH inhibited IP3-induced Ca^<2+> release actibated by phenyrephrine without any effects on Ca^<2+>-induced Ca^<2+> release activated by caffeine. PTH decreased a contraction evoked by high K without inhibitory effects on changes in [Ca^<2+>] in, suggesting that PTH has a direct inhibitory effect on the contractile machinery. Intracellular signal trasduction by the PTH receptor may be coupled with increases in cyclic AMP by the activation of the adenylate cyclase. 3. The characteristics of IP3-induced Ca^<2+> release and the source of Ca^<2+> taken up into Ca^<2+> stores were examined in the intestinal smooth muscle. Ca^<2+> released from the store activated not only the contractile machinery but also Ca^<2+>-activated K^+ channels. Ca^<2+> stores seem to take up into Ca^<2+> preferentially passing through unique Ca^<2+> channels, but not voltage-dependent Ca^<2+> channels. PTH may affect the Ca^<2+> release and/or Ca^<2+> uptake through cyclic AMP-dependent pathways.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Shigeo Ito: "Inositol 1,4,5-trisphosphate-induced Ca^<2+>-transient and outward K^+ current in single smooth muscle cells of guinea pig small intestine" Japnese Journal of Pharmacology. 71. 1-10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mitsuyasu Tabo: "Effects of external K^+ on depletion-induced Ca^<2+> entry in rat ileal smooth muscle." European Journal of Pharmacology. 313. 151-158 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ito: "Characteristics of carbachol-and caffeine-induced inward currents in rat intestinal smooth muscle cells." Smooth Muscle Excitation, Fds. Bolton T. B. & Yomita T., Academic Press, London. 187-196 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ito: "Inositol 1,4,5-trisphosphate-induced Ca^<2+>-transient and outward K^+ current in single smooth muscle cells of guinea pig small intestine." Japanese Journal of Pharmacology. 71. 1-10 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mitsuyasu Tabo: "Effects of external K^+ on depletion-induced Ca^<2+> entry in rat ileal smooth muscle." European Journal of Pharmacology. 313. 151-158 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ito: Characteristics of carbachol-and caffeine-induced inward currents in rat intestinal smooth muscle cells. Smooth Muscle Excitation, Eds.Bolton T.B.& Tomita T.Academic Press, London, 187-196 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shigeo Ito: "Inositol 1,4,5-trisphosphate-induced Ca^<2+>-transient and outward K^+ current in single smooth muscle cells of guinea pig small intestine." Japanese Journal of Pharmacology. 71. 1-10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mitsuyasu Tabo: "Effects of external K^+ on depletion-induced Ca^<2+> entry in rat ileal smooth muscle." European Journal of Pharmacology. 313. 151-158 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shigeo Ito: "Characteristics of carbachol-and caffeine-induced inward currents in rat intestinal smooth muscle cells." Smooth Muscle Excitation,Eds. Bolton T. B. & Tomita T. , Academic Press, London. 187-196 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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