| Project/Area Number |
05454577
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | Yokohama City Univ. |
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Principal Investigator |
UEDA Hiroshi Yokohama City University Pharmacology Associate Professor, 医学部, 助教授 (00145674)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMAE Takeaki Yokohama City University Pharmacology Instructor, 医学部, 助手 (00239435)
FUKUSHIMA Nobuyuki Yokohama City University Pharmacology Instructor, 医学部, 助手 (10254161)
GOSHIMA Yoshio Yokohama City University Pharmacology Lecturer, 医学部, 講師 (00153750)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | Opioid receptor / Signal transduction / Xenopus Laevis / Oocytes / Cloning / G-protein / 〓イノフィンACセプター / オピオイドレセプター / 情報伝達 / 母細胞 / 発現クローニング |
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| Research Abstract |
Here we report the evidence for a novel type of opioid kappa-receptor inhibiting G-protein activity in the guinea pig cerebellum. In guinea pig cerebellar membranes, kappa-agonists inhibit the high-affinity GTPase activity in concentrations lower than those for stimulation of this activity, possibly through known 7-transmembrane type of opioid kappa-receptor. The inhibitory activity was found to be attributed to the direct inhibition of GTP-GDP exchange activity on Gil reconstituted into membranes. Taken into consideration the finding that kappa-receptor agonists inhibit phospholipase C through an inhibition of Gil activity, we attempted to clone this metabostatic receptor which inhibits currents mediated through Gil and phospholipase C in Xenopus oocytes. In Xenopus oocytes coinjected with RNAs of metabotropic glutamate receptor (or muscarinic M2 receptor) and Gila, the kappa-receptor agonists inhibits these metabotropic receptor-mediated currents. These inhibitory effects were completely antagonized by norBNI,an opioid kappa-receptor antagonist. Using conventional strategies, we cloned a novel type of metabostatic kappa-receptor which has no apparent transmembrane domain.
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