2003 Fiscal Year Final Research Report Summary
Analysis of opioid receptors and substance P activity in signal transduction and inflammation
| Project/Area Number |
13671615
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
NISHIMURA Kinya Juntendo University School of Medicine, associate Professor, 医学部, 助教授 (80164581)
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| Co-Investigator(Kenkyū-buntansha) |
WARABI Kengo Juntendo University School of Medicine, assistant Professor, 医学部, 助手 (30311989)
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| Project Period (FY) |
2001 – 2003
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| Keywords | G protein / Spinorphin / LTP / Stnatum / substance P |
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| Research Abstract |
We found an endogenous factor that modulated enkephalin-degrating activity and purified it from bovine spinal cord based on its inhibitory activity toward enkephalin-degrading enzymes. Structural analysis revealed the factor to be Leu-Val-Tyr-Pro-Trp-Thr and it was named spinorphin. It has been found that spinorphin inhibited the activity toward various enkephalin-degrating enzymes from monkey brain, especially dipeptidyl peptidase III. Recently we found that this inhibitory significantly inhibited bradykin-induced nociceptive flexor responses. We also have reported roles for spinorphin in inflammation. Spinorphin significantly inhibited the functions of polymorphonuclear neutrophils by suppressing the binding of fMLF to its receptor on PMNs. The possible role of spinorphin as reglulators in pain and inflammation will be discussed.
G protein coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors, leading to receptor desensitization. We investigated whether human substance P receptor is a substrate of GRK5. We report that human Substance P receptor is phosphorylated by purified GRK5. The phosphorylation has a high stoichiometry and a low Km. These data provide the first evidence that human substance P receptor is a substrate of GRK5.
Although the importance of Ach in the learning and memory processes has been point out in the stratum as well as the cerebral cortex. The aim of our study was to answer this question using the striatal cholinergic inter-neurons and to elucidate the mechanism of synaptic plasticity in them. The results obtained here indicate the following. Electrical stimulation of cortico/thalamostriatal pathway frequently evokes a depolarizing and hyperpolarizing postsynaptic potential in the cholinergic inter-neurons that is composed of a cortic/thalamostriatal glutamatergic EPSP and an intrastriatally evoked disynaptic GABAergic IPSP, respectively.
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