| Project/Area Number |
07407080
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ICHIKAWA Atsushi Kyoto Univ., Fac.Pharmaceutical Sci., Professor, 薬学部, 教授 (10025695)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Yukihiko Kyoto Univ., Fac.Pharmaceutical Sci., Assistant, 薬学部, 助手 (80243038)
NEGISHI Manabu Kyoto Univ., Fac.Pharmaceutical Sci., Associate Professor, 薬学部, 助教授 (60201696)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1996: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | arachidonic acid / prostanoid / postaglandin receptor / 7th transmembrane receptor / GTP binding protein / signal transduction / gene targetting / structure-activity relationship / プロスタノイド受容体 / G蛋白活性化ドメイン / 後根神経節 / 成熟胸腺細胞 / 動脈平滑筋 |
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| Research Abstract |
In order to clarify the molecular actions of prostaglandins, it needs to clone their receptor cDNAs and studied the structures and functions of their receptors in expressed cells, and to examine the phenotypic appearance of their receptor knock-out mice. In this project, we have obtained the following results ; (1) we cloned at least 6 kinds (EP1, EP2, EP3, EP4, FP,IP) of mouse PG receptor cDNAs. (2) In expressed CHO cells, we examined the functional domains of PG receptor for binding sites and signaling via G protein coupling. (3) In EP3 receptor, we showed the hydrogen bonding interation of carbonyl residue of EP3 agonists and residue 309 arginine in 7th transmembrane domain of EP3 receptor is sufficient for the functional activation. (4) This interaction is essential for the activation of Gs and Gq but not Gi in EP3D receptor. (5) we have prepared some knock-out mice which are deficient in PGF (FP) receptor and EP2/EP4 receptors. (6) FP knock-out mice revealed the loss of delivery of growing fetus. The mechanism is supposed to be involved in the deficient of PGF action in the regression of corpus luteum. (7) We have been making EP2 and EP4 knock-out mice. EP4 knock-out mice has a severe phenotypic appearance, since they die during 1-2 days after birth because of the deficient function of vascular circulation.
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