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Structural Organization and Transcriptional Regulation of the Human beta_1-Adrenergic Receptor Gene

Research Project

Project/Area Number 01440048
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

MATSUI Hiroaki  ST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF NEUROPSYCHIATRY, LECTURER, 医学部, 講師 (90181685)

Co-Investigator(Kenkyū-buntansha) INO Miyuki  ST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF NEUROPSYCHIATRY, ASSIS, 医学部, 助手 (20203218)
朝倉 幹雄  聖マリアンナ医科大学, 医学部, 助教授 (70103504)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1991: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1990: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1989: ¥14,300,000 (Direct Cost: ¥14,300,000)
Keywordsbeta_1-adrenergic receptor / antidepressant / receptor regulation / receptor gene expression / βーアドレナリン受容体 / 受容体遺伝子発現調節 / 抗うつ薬作用機序 / βアドレナリン受容体 / 受容体遺伝子発現調節機構
Research Abstract

To investigate the effects of antidepressant treatment on the beta_1-adrenergic receptor(AR) at transcriptional levels, the delineation of the structural organization of the human beta_1-AR gene was attempted. A genomic clone was obtained from human placental genomic library through repeated screenings using the 1.3-kb(kilobase) Smal fragment human beta_1-AR cDNA(complementary DNA) probe. Restriction endonuclease fragments of interest were subcloned into pUC18 and sequenced by the dideoxy chain-termination method.
The proximal promoter region (-1300 through -50 relative to the adenosine of the first methionine codon) lacks TATA box, is rich in G + C content, and has multiple putative binding sites for transcriptional factor Sp1 and AP-2. Thus, the proximal promoter region has features of "house- keeping" genes.
The distal promoter region (-2300 through -1300) has representative TATA box and CAAT box consequences, typical thyroid, estrogen, glucorticoid, cAMP responsive el'ements, and binding sites for transcriptional factor AP-1, GATA-1,2.3, which indicate multiple regulatory mechanisms involved in the beta_1-AR gene expression in vivo. Moreover, there is present in the human genome a long [1032-bp(base pair)] open reading frame which ends only 112-bp 5' to the initiator methionine of the receptor, and which encodes a putative protein of the molecular weight of - 38000.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report

Research Products

(25 results)

All Other

All Publications (25 results)

  • [Publications] 足立 淳,: "ヒトB_1アドレナリン受容体遺伝子の分子クローニグおよびその構造解析." 神経化学. 31. 594-595 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 足立 淳: "ヒトβ_1アドレナリン受容体遺伝子の分子クローニングおよびその構造解析" 聖マリアンナ医科大学誌,. 20,. 246-261 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] A.Sato.: "Effects of long-term treatment with serotonergic agonists and antagonists on 5-HT1A receptors in the rat brain." The Japanese J.Psychiat.Neurol.45,. 753 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松井 宏晃,: "アミロイドβ蛋白質前駆体遺伝子の発現調節機構:プロテインキナーゼCの関与." 長寿科学総合研究・痴呆性疾患の遺伝学研究平成2年度研究報告書. 1,. 117-118 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 朝倉 幹雄,: "抗うつ薬投与後のラット脳内存性蛋白質のCa^<2+>/リン脂質依存性蛋白質リン酸化." 精神薬療基金研究年報,. 22,. 163-168 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 足立 淳,: "ラット大脳皮質におけるα_1アドレナリン受容体サブタイプの結合特性-金属およびヌクレオチドの影響." 薬物・精神・行動,. 10,. 120 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 長田 賢一,: "膜結合型プロティンキナーゼCに対するフォルボールエステル結合特性." 薬物・精神・行動,. 10,. 204 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 足立 淳,: "ラット大脳皮質におけるα_1アドレナリン受容体サブタイプの結合特性-抗精神病薬および抗うつ薬の影響." 薬物・精神・行動,. 10,. 508 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H.Matsui: "Localization of the fourth membrane spanning domain as a ligand binding site in the human Platelet α_2 ^-adrenrgic receptor." Biochemistry.28. 4125-4130 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J.W.Regan: "Receptor Biochmistry" (L.L.LImbird ed.,IRL Press),22 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松井 宏晃,: "精神分裂病-基礎と臨床" (木村 敏也編,朝倉書吉), 9 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松井 宏晃: "神経生化学" (日本生化学会編,東京化学同人), 10 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atsushi Adachi: "Molecular cloning and structural organization of the human beta_1-adrenergic receptor gene." Bulletin of the Japanese Neurochemical Society. 31. 594-595 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atsuko Sato: "Effects of long-term treatment with serotonergic agonists and antagonists on 5-HT1A receptors in the rat brain." The Japanese J. Psychiat. Neurol.45. 753 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atsushi Adachi: "Binding characteristics of the alpha_1-adrenergic receptor subtypes in the rat brain:effects of cations and nucleotides." Japanese J. Psychopharmacology. 10. 120 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kenichi Osada: "Effects of phorbol ester on the membrane-inserted protein kinase C." Japanese J. Psychopharmacology. 10. 204 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Atsushi Adachi: "Binding characteristics of the alpha_1-adrenergic receptor subtypes in the rat brain:effects of antipsychotics and antidepressants." Japanese J. Psychopharmacology. 10. 508 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroaki Matsui: "Localization of the fourth membrane spanning domain as a ligand binding site in the human platelet alpha_2-adrenergic receptor." Biochemistry. 28. 4125-4130 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J.W. Regan: "alpha_2-adrenergic receptor purification." (in Receptor Biochemistry, L.L.Limbird ed., IRL Press). 141-161 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroaki Matsui: "Delineation of the intronless nature of the gene for the human betaー1 adrenergic receptor and the structural organization of the putative promotor." FEBS Letters.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroaki Matsui: "Effects of the chronic antidepressant treatment on the transcriptional regulation of the betaー1 adrenergic receptor gene." FEBS Letters.

    • Related Report
      1991 Annual Research Report
  • [Publications] Atsushi Adachi: "Evidence for the involvement of guanine nucleotide binding proteins in the regulation of α_1Aーand α_1Bーadrenergic receptors in the rat cerebral cortex." European Neuropsychopharmacology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroaki Matsui: "Delineation of the intronless nature of the genes for the human and rat β_1ーadrenergic receptor and their putative promotor regions." Proc.Nat.Acad.Sci.U.S.A.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroaki Matsui: "Effects of chronic antidepressant treatment on the transcription of β_1ー,β_2ー,α_<1A>ーand α_1Bーadrenergic receptor genes in the rat brain." J.Neurochemistry.

    • Related Report
      1990 Annual Research Report
  • [Publications] Atsushi Adachi: "Evidence for the possible involvement of guanine nucleotide binding proteins in the regulation of alpha1A and alpha1B-adrenergic receptors in the rat cerebral cortex" European Journal of Pharmacology,molecular pharmacology section.

    • Related Report
      1989 Annual Research Report

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Published: 1989-03-31   Modified: 2016-04-21  

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