| Project/Area Number |
01440048
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | ST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
MATSUI Hiroaki ST. MARIANNA UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF NEUROPSYCHIATRY, LECTURER, 医学部, 講師 (90181685)
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| 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)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| 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)
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| Keywords | beta_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 |
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| 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.
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