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Desensitization of prostaglandin receptors

Research Project

Project/Area Number 02807202
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKyoto University

Principal Investigator

YATSUNAMI Kimio  Kyoto University, Pharmacology, Assistant, 薬学部, 助手 (30191141)

Co-Investigator(Kenkyū-buntansha) ICHIKAWA Atsushi  Kyoto University, Pharmacology, Professor, 薬学部, 教授 (10025695)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsProstaglandin E / prostacyclin / desensitization / receptor / GTP binding protein / GTP / Mastocytoma cells
Research Abstract

We have investigated the mechanism of desensitization of receptors for prostaglandin E_1 and for l_2 (prostacyclin). When the membranes were preincubated with[ ^3H] PGE_1 for 60 min at 37゚C. the dissociation of the ligand form the receptor was remarkably decreased, even in the presence of GTPgammaS. The stable[ ^3H]PGE_1-bound receptor complex was solubilized with 6% digitonin. The solubilized[ ^3H]PGE_1 receptor was eluted with[ ^<35>S]GTPgammaS binding activity from an Ultrogel AcA44 column. The fractions containing activities of both[ ^3H]PGE_1 and[ ^<35>S]GTPgammaS bindings were further purified by column chromatographies on wheat germ agglutinin(WGA)-agarose and phenyl-Sepharose CL-4B. The partially purified[ ^3H]PGE_1-bound receptor was affinity-labeled with [ ^<14>C]5'-P-fluorosulfonylbenzoylguanosine and a protein with a molecular mass of 60 kDa was detected.
Iloprost, a stable prostacyclin analogue, transiently stimulated adenylate cyclase activity. floprost also induced the translocation of alpha subunits(42- and 45-kDa)of stimulatory guanine nucleotide-binding proteins(Gsalpha)from the membrane to the cytosol. These results taken together demonstrate the the desensitization of prostaglandin receptors, 'are caused by distinct mechanisms between those of prostaglandin E_1 and prostacyclin.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kimio Yatsunami: "Eicosanoida and their receptors" Seikagaku. 62. 343-348 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kimio Yatsunami: "Effect of tunicamycin on functions of PGE_1 receptors from mouse mastocytoma P-815 cells" Biochimica et Biophysica Acta. 1051. 94-99 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kazuhiro Kimura: "Stimulatory effect of guanine nucleotides on prostaglandin E_1 binding to murine renal outer medulla" J. Pharmacobio-Dyn.14. 53-60 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satoru Takahashi: "Characterization of cytosolic pertussis toxin-sensitive GTP-binding protein in mastocytoma P-815 cells" Biochimica et Biophysica Acta. 1093. 207-215 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Prostaglandin E_1 receptor from mouse mastocytoma P-815 cells couples to 60 kDa GTP-binding protein" Biochimica et Biophysica Acta. 1095. 140-144 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Manabu Negishi: "TEI-9063,a stable and highly specific prostacyclin analogue for the prostacyclin receptor in mastocytoma P-815 cells" Prostaglandins. 42. 225-237 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kimio Yatsunami: "Eicosanoids and their receptors" Seikagaku. 62. 343-348 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kimio Yatsunami: "Effect of tunicamycin of functions of PGE_1 receptors from mouse mastocytoma P-815 cells" Biochim. Biophys. Acta. 1051. 94-99 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kazuhiro Kimura: "Stimulatory effect of guanine nucleotides on prostaglandin E_1 binding to murine renal outer medulla" J. Pharmacobio-Dyn.14. 53-60 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satoru Takahashi: "Characterization of cytosolic pertussis toxin-sensitive GTP-binding protein in mastocytoma P-815 cells" Biochim. Biophys. Acta. 1093. 207-215 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Prostaglandin E_1 receptor from mouse mastocytoma P-815 cells couples to 60 kDa GTP-binding protein" Biochim. Biophys. Acta. 1095. 140-144 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Manabu Negishi: "TEI-9063, a stable and highly specific prostacyclin analogue for the prostacyclin receptor in mastocytoma P-815 cells" Prostaglandins. 42. 225-237 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kazuhiro Kimura: "Inhibition of prostaglandin E_2ーinduced cAMP formation by phorbolester in MDBK cells" Biochem.Pharmacol.(Life Sci.Adv.). 9. 45-53 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kazuhiro Kimura: "Stimulatory effect of guanine nucleotides on prostaglandin E_1 binding to murine renal outer medulla" J.PharmacobioーDyn.14. 53-60 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Satoru Takahashi: "Characterization of cytosolic pertussis toxinーsensitive GTPーbinding protein in masカocytoma Pー815 cells" Biochimica et Biophysica Acta. 1093. 207-215 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hitoshi Hashimoto: "Prostaglandin E_1 receptor from mouse mastocytoma Pー815 cells couples to 60 kDa GTPーbinding protein" Biochimica et Biophysica Acta. 1095. 140-144 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Manabu Negishi: "TEIー9063,a satble and highly specific prostacyclin analogue for the prostacyclin receptor in mastocytoma Pー815 cells" Prostaglandins. 42. 225-237 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hitoshi Hashimoto: "Prostaglandin E_1 receptor from mouse mastocytoma Pー815 cells couples to a 60ーkDa GTPーbinding protein" Biochemical Biophysical Research Communications.

    • Related Report
      1990 Annual Research Report
  • [Publications] Kimio Yatsunami: "Eicosanoids and their receptors" Seikagaku. 62. 343-348 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kimio Yatsunami: "Effect of tunicamycin on functions of PGE_1 receptors from mouse mastocytoma Pー815 cells" Biochimica Biophysica Acta. 1051. 94-99 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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