1989 Fiscal Year Final Research Report Summary
Cellular mechanism of long-term modulatory synaptic changes (1989)
| Project/Area Number |
62570064
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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 | Tokyo Medical College |
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Principal Investigator |
KOBAYASHI Haruo Tokyo Med. Coll., Sch. Med., Professor, 医学部, 教授 (20074502)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Susumu Yamaguchi Univ., Sch. Lib. Arts., Professor, 教養部, 教授 (90022665)
MOCHIDA Sumiko Tokyo Med. Coll., Sch. Med., Assist. Prof., 医学部, 講師 (30096341)
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| Project Period (FY) |
1987 – 1989
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| Keywords | sympathetic ganglion / synoptic transmission / muscarinic receptors / cyclic GMP / protein phosphorylation / intracellular signal transduction / plasticity / long-term enhancement |
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| Research Abstract |
Superior cervical ganglia (SCG) of rabbits were mainly used in this research project.
1) Slow muscarinic depolarizing postsynaptic potentials were durably enhanced following brief exposure of the ganglion to dopamine. Similar long-term enhancement (LTE) was also produced by a treatment with cyclic AMP. Antagonists of D_1-dopaminergic receptors blocked both of the production of LTE and cAMP synthesis. These suggest that activation of D_1-receptors causes in sympathetic neurons an elevation of cAMP which in turn produces some enduring neuronal change that underlies an amplification of the muscarinic depolarizing synoptic response.
2) Cyclic GMP-dependent protein kinase (G-kinase) activity was detected in SCG and two endogenous substrate proteins (90K and 54K) were identified. Phosphorylation of these proteins were increased following activation of M_1-muscarinic receptors. It is likely that cGMP-dependent protein phosphorylation system may be involved as an intracellular signal transduction process for the generation of slow muscarinic depolarizing synoptic response.
3) Activation of M_2-muscarinic receptors caused a depression of Ca^<2+> influx during action potentials. This muscarinic effect appeared to be mediated by phosphatidylinositol breakdown and subsequent activation of C-kinase system.
4) Various muscarinic trans-synaptic events have been shown in this study to be coupled to the different intracellular transduction systems and operated different neuronal functions.
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