2005 Fiscal Year Final Research Report Summary
Identification of the endocannabinoid working as a retrograde messenger and its release mechanism
| Project/Area Number |
15300133
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHOSAKU Takako Kanazawa University, Graduate School of Medical Science, Professor, 医学系研究科, 教授 (60179025)
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| Co-Investigator(Kenkyū-buntansha) |
KANO Masanobu Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (40185963)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Endocannabinoid / Phospholipase C / Calcium ion / Retrograde signal / Hippocampal neuron / Synaptic modulation / Metabotropic glutamate receptor / Muscarinic receptor |
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| Research Abstract |
Recent studies have revealed that endocannabinoids work as a retrograde messenger and play an important role in activity-dependent modulations of synaptic transmission in the brain. The endocannabinoid release is induced by postsynaptic depolarization or activation of group I metabotropic glutamate receptors (I-mGluRs). The released endocannabinoid then activates presynaptic CB1 cannabinoid receptors and suppresses the transmitter release. The mechanisms of endocannabinoid production, however, have not been fully determined. In this study, we used rat cultured hippocampal neurons and recorded cannabinoid-sensitive inhibitory postsynaptic currents (IPSCs), which can be used as biosensor of released endocannabinoids. We obtained the following results.
1.Among three candidates of endocannabinoids (anandamide,2-AG, noladin ether),2-AG was the most effective and reversible in suppressing IPSCs.
2.The endocannabinoid release was induced by postsynaptic activation, of M1/M3 muscarinic receptors
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as well as I-mGluRs. This receptor-driven endocannabinoid release was eliminated from the neurons prepared from PLCβ1-knockout mice.
3.The depolarization-induced endocannabinoid release, which is dependent on Ca^<2+> elevation, was suppressed by the PLC inhibitor ET-18,but not eliminated from PLCβ1- or PLCδ-knockout mice.
4.When weak depolarization and weak activation of I-mGluRs or M1/M3 muscarinic receptors, both of which can not induce endocannabinoid release, were simultaneously treated, endocannabinoids were released. This type of release was also eliminated from PLCβ1-knockout mice. Using TRPC6 channels as biosensor of PLC activity, we demonstrated that the synergistic effect of depolarization and receptor activation on endocannabinoid release can be explained by the Ca^<2+>-dependence of receptor-driven PLCβ activation.
These results suggest that the postsynatpic activation (depolarization or receptor activation) stimulates PLCs and induces 2-AG production through the subsequent enzymatic activity by DAG lipase. The isozymes of PLCs involved might be different in different stimulation conditions. Less
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[Journal Article] The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum.2006
Author(s)
Kawamura, Y., Fukaya, M., Maejima, T., Yoshida, T., Miura, E., Watanabe, M., Ohno-Shosaku, T., Kano, M.
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Journal Title
J.Neurosci. 26
Pages: 2991-3001
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Phospholipase Cbeta serves as a coincidence detector through its Ca^<2+> dependency for triggering retrograde endocannabinoid signal.2005
Author(s)
Hashimotodani, Y., Ohno-Shosaku, T., Tsubokawa, H., Ogata, H., Emoto, K., Maejima, T., Araishi, K., Shin, H.-S., Kano, M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phosphokipase C beta4 signaling cascade in the cerebellum.2005
Author(s)
Maejime, T., Oka, S., Hashimotodani, Y., Ohno-Shosaku, T., Aiba, A., Wu, D., Waku, K., Sugiura, T., Kano, M.
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Journal Title
J.Neurosci. 25
Pages: 6826-6835
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Control of synaptic transmission in the CNS through endocannabinoid-mediated retrograde signaling.2005
Author(s)
Ohno-Shosaku, T., Maejima, T., Yoshida, T., Hashimoto, K., Fukudome, Y., Kano, M.
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Journal Title
Dendritic Neurotransmitter Release. (Springer Science+Business Media, Inc.)
Pages: 269-281
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two distinct classes of muscarinic action on hippocampal inhibitory synapses : M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling.2004
Author(s)
Fukudome, Y., Ohno-Shosaku, T., Matsui, M., Omori, Y., Fukaya, M., Tsubokawa, H., Taketo, M.M., Watanabe, M, Manabe, T., Kano, M.
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Journal Title
Eur.J.Neurosci. 19
Pages: 2682-2692
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel action of stargazin as an enhancer of AMPA receptor activity.2004
Author(s)
Yamazaki, M., Ohno-Shosaku, T., Fukaya, M., Kano, M., Watanabe, M., Sakimura, K.
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Journal Title
Neurosci.Res. 50
Pages: 369-374
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus.2003
Author(s)
Ohno-Shosaku, T., Matsui, M., Fukudome, Y., Shosaku, J., Tsubokawa, H., Taketo, M.M., Manabe, T., Kano, M.
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Journal Title
Eur.J.Neurosci. 18
Pages: 106-116
Description
「研究成果報告書概要(欧文)」より
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