| Project/Area Number |
10470009
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
AKAIKE Norio Graduate School of Medical Sciences, Kyushu University, Professor, 大学院・医学系研究科, 教授 (30040182)
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| Co-Investigator(Kenkyū-buntansha) |
RHEE Jeong seop Graduate School of Medical Sciences, Kyushu University, Assistant Professor, 大学院・医学系研究科, 助手 (50294913)
NABEKURA Junichi Graduate School of Medical Sciences, Kyushu University, Associate Professor, 大学院・医学系研究科, 助教授 (50237583)
野田 百美 九州大学, 医学部, 助手 (80127985)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | Calmodulin / Hippocampus / Patch Clamp / adenyl cydlase / IPィイD23ィエD2 / Calcium / glycine / パソプレッシン / V1、V2受容体 / 細胞内情報伝達系 / PKA / Ca^<2+> / CaMは依存性アデニールサイクレース / グリシン応答 |
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| Research Abstract |
To explore the intracellular pathways activated by vasopressin receptors, the effects of arginine vasopressin (AVP) and its analogs mediating glycine (Gly)-induced Cl- currents (lィイD2GlyィエD2) were examined in acutely dissociated rat hoppocampal CA1 neurons using the while-cell patch recording technique. AVP and its analogs inhibited lィイD2GlyィエD2 in a concentration-dependent manner. The inhibitory actions of AVP (4-9) [AVP metabolite] and NC-1900 [AVP (4-9) analog] were reversed by a VィイD21ィエD2 receptor antagonist, or pretreatment with BAPTA-AM. In contrast, these blocking procedures had no effect on the DDAVP [VィイD22ィエD2 agonist] action. A VィイD22ィエD2 receptor antagonist did not block the inhibitory action of AVP(4-9) or NC-1900, but blocked that of DDAVP. The inhibitory action of AVP was completely blocked by the co-application of the VィイD21ィエD2 and VィイD22ィエD2 antagonists. The inhibitory action of NC-1900 was not affected by perfusion with a CaィイD12+ィエD1-free external solution, but was strongly blocked by thapsigargin. The intercellular application of heparin of anti-IPィイD23ィエD2 also blocked the NC-1900 action. Furthermore, CaィイD12+ィエD1/calmodulin (CaM) inhibitors blocked the NC-1900 action, while a Cam-dependent kinase II inhibitor and PKC modulators had no effect. 2', 5'-Dideoxyadenosine, an adenylate cyclase inhibitor, H-89 and Rp-cAMPS blocked the inhibitory actions of NC-1900 and DDAVP. These results suggest that the activation of the VィイD21ィエD2 receptor in the hippocampal neurons induces the production of IPィイD23ィエD2 which releases CaィイD12+ィエD1 from the IPィイD23ィエD2-sensitive CaィイD12+ィエD1 storage sites. The CaィイD12+ィエD1 binds to CaM, resulting in the activation of CaィイD12+ィエD1/CaM-sensitive adenylate cyclases. The activation of PKA through the adenylate cyclase inhibits lィイD2GlyィエD2.
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