Molecular Biological Studies on Mechanisms Underlying Long Term Potentiation in Hippocampus Induced by a Bee Venom.
| Project/Area Number |
01570064
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Osaka University |
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Principal Investigator |
IKENAKA Kazuhiro Osaka University, Institute for Protein Research, Associate Professor, たんぱく質研究所, 助教授 (00144527)
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| Co-Investigator(Kenkyū-buntansha) |
AIMOTO Saburo Osaka University, Institute for Protein Research, Associate Professor, 蛋白質研究所, 助教授 (80029967)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | MCD Peptide / Hippocampus / Long-term Potentiation / Potassium Channel / GTP-binding protein / 長期増強効果 / ペプチド合成 / NMDAチャネル |
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| Research Abstract |
A bee venom, mast cell degranulating (MCD) peptide, was synthesized by stepwise formation of the two disulfide bridges. This synthetic MCD peptide induced long-term potentiation (LTP) in the CA1 region of hippocampus slice at concentrations ranging from 10^<-7> to 10^<-5> M.
NMDA receptor is known to be involved in LTP induced by trains of high frequency electric stimulation (tetanus stimulation). We added several NMDA-antagonists (APV or MK-801) to the reaction bath, however, induction of LTP by MCD was not inhibited. This result suggests that the pathways leading to LTP-induction are quite different between the two stimuli ; tetanus and MCD.
We found that MCD possesses multiple functions. (1) Binding and thereby inhibiting a voltage dependent K^+ channel in brain membranes. (2) Interaction with lipid bilayer to form voltage dependent and cation selective channels by itself. (3) Activation of a pertussis toxin-sensitive GTP-binding protein in mast cells. Ih this study, we prepared several derivatives and analogs of MCD and investigated which function is more closely related to the induction of LTP. Another bee venom, apamin, formed ion channels in lipid bilayer which was indistinguishable from that formed by MCD. D-MCD, an otic isomer of MCD, and diiodo-MCD activated a pertussis toxin-sensitive GTP-binding protein. However, these peptides did not induce LTP in the hippocampus slices. A snake venom, dendrototoxin-l, bound to the same K+channels as MCD and it did induce LTP. These results indicated that the most potent aspect of MCD involved in LTP-inducibility was its interaction with the voltage dependent K^+ channel.
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Report
(3 results)
Research Products
(19 results)
