| Project/Area Number |
05404020
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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 |
Pathological medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NARUMIYA Shuh Kyoto University, Faculty of Medicine, Department of Pharmacology, Professor, 医学研究科, 教授 (70144350)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Masakazu Kyoto University, Faculty of Medicine, Department of Pharmacology, Assistant Pro, 医学研究科, 助手 (40261143)
MOMIYAMA Toshihiko Kyoto University, Faculty of Medicine, Department of Pharmacology, Assistant Pro, 医学研究科, 助手 (20230055)
USHIKUBI Fumitaka Kyoto University, Faculty of Medicine, Department of Pharmacology, Associate Pro, 医学研究科, 講師 (50243035)
KAKIZUKA Akira Kyoto University, Faculty of Medicine, Department of Pharmacology, Associate Pro, 医学研究科, 助教授 (80204329)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥32,800,000 (Direct Cost: ¥32,800,000)
Fiscal Year 1995: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1994: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1993: ¥22,700,000 (Direct Cost: ¥22,700,000)
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| Keywords | prostaglandin / thromboxane receptor / ligand binding / signal transduction / receptor isoform / gene receptor / receptor distribution / receptor abnormality / プロスタノイド受容体分子進化 / プロスタサイクリン受容体体内分布 / トロンボキサン受容体アイソフォーム / ラット脳EP_3受容体 / プロスタグランジン受容体遺伝子 / プロスタグランジン / トロンボキサン / 受容体 / G蛋白質 / 情報伝達 / 血小板異常症 / 脳内分布 / 遺伝子 / アポプトーシス / 胸腺 |
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| Research Abstract |
1.cDMAs for six types and subtypes of the prostanoid receptors of various species were cloned by the use of the cDNAs and nucleotide sequences of the thromboxane (TX) receptor (TP) and the prostaglandin (PG) E receptor EP3 subtype (EP3) we previously cloned. They include PGD receptor (DP) , PGE receptor EP1, EP2 and EP4 subtypes, PGF receptor (FP) and PGI receptor (IP) . Their structures, ligand binding specificities and signal transduction pathways were characterized.
2.Genetic loci of these receptor genes on mouse chromosomes were determined, and gene structures of the human TP and IP were elucidated.
3.The receptor isoforms of EP3 and TP created by altemative splicing were found. They were different only in the C-terminal tail but different in the signal transduction pathways.
4.Distribution of these receptors in the body was revealed by northem blot analysis, and the detailed analysis by in situ hybridization were carried out for IP in mouse, for EP3 in mouse brain and for PGE receptor subtypes in mouse kidney. Specific functions were examined for TP in mouse thymus and in liver, and EP2 and EP3 in mouse brain.
5.A point mutation was found in TP in patients with inherited bleeding disorder and identified as a cause of this disease.
This work has thus clucidated molecular structures of all of the eight prostanoid receptors and provided the molecular basis for diverse physiological actions of the prostanoid molecules.
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