Effect of Synthetic Cell-Penetrating Peptides on TrkA Activity in PC12 Cells
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概要
- 論文の詳細を見る
As TrkA, a high-affinity receptor of nerve growth factor (NGF), is a potential target for relieving uncontrolled inflammatory pain, an effective inhibitor of TrkA has been required for pain management. To identify a specific inhibitor of TrkA activity, we designed cell-penetrating peptides combined with amino-acid sequences in the activation loop of TrkA to antagonize tyrosine kinase activity. To select a peptide inhibiting TrkA activity, we examined the effect of cell-penetrating peptides on tyrosine kinase activity of recombinant TrkA in vitro and studied their effects on NGF-stimulated neurite outgrowth and protein phosphorylation in PC12 cells. Thereafter we investigated the effect of the selected peptide on NGF-stimulated TrkA activity and the expression of transient receptor potential channel 1 in PC12 cells. The selected peptide inhibited TrkA activity, but did not inhibit tyrosine kinase activities of other receptor-type tyrosine kinases in vitro. It also suppressed NGF-stimulated responses in PC12 cells. The selected synthetic cell-penetrating peptide antagonizing TrkA function would be a candidate for inflammatory pain therapy.
- 社団法人 日本薬理学会の論文
- 2008-01-20
著者
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SAKAGUCHI Masahiro
Department of Veterinary Microbiology, School of Veterinary Medicine, Azabu University
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Murata Eri
Department of Anesthesiology and Reanimatology, University of Fukui, Faculty of Medical Sciences, Ja
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Ueda Koyo
Department of Anesthesiology and Reanimatology, University of Fukui, Faculty of Medical Sciences, Ja
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Kuroda Yoshihiro
Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo Universi
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Abe Mineo
Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
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Shigemi Kenji
Department of Anesthesiology and Reanimatology, University of Fukui, Faculty of Medical Sciences, Ja
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Hirose Munetaka
Department of Anesthesiology and Reanimatology, University of Fukui, Faculty of Medical Sciences, Ja
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TANAKA Yoshifumi
Department of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Me
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Tanaka Yoshifumi
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Abe Mineo
Graduate School Of Pharmaceutical Sciences Kyoto University
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Shigemi Kenji
Department Of Anesthesiology And Reanimatology Faculty Of Medical Sciences Fukui University
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Kuroda Yoshihiro
Department Of Pharmaceutical Health Care Faculty Of Pharmaceutical Sciences Himeji Dokkyo University
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HIRATA MASASHI
Department of Agricultural Chemistry, Faculty of Bioresources, Mie University
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Hirata Masashi
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Hirata Masashi
Department Of Agricultural Chemistry Faculty Of Bioresources Mie University
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Sakaguchi Masahiro
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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TAKATORI Mayumi
Department of Anesthesiology, Kyoto Prefectural University of Medicine
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ISADA Tetsuro
Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University
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SHIBAZAKI Masayuki
Department of Anesthesiology, Kyoto Prefectural University of Medicine
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SHIMIZU Fumihiro
Department of Anesthesiology, Kyoto Prefectural University of Medicine
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FUKAZAWA Keita
Department of Anesthesiology, Kyoto Prefectural University of Medicine
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KAGEYAMA Kyoko
Department of Anesthesiology, Kyoto Prefectural University of Medicine
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Isada Tetsuro
Department Of Anesthesiology And Reanimatology Faculty Of Medical Sciences Fukui University
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Kageyama Kyoko
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Kageyama Kyoko
Department Of Anesthesiology Kyoto Prefectual University Of Medicine
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Fukazawa Keita
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Murata Eri
Department Of Anesthesiology And Reanimatology Faculty Of Medical Sciences University Of Fukui
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Ueda Koyo
Department Of Anesthesiology And Reanimatology Faculty Of Medical Sciences University Of Fukui
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Takatori Mayumi
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Shimizu Fumihiro
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Shibazaki Masayuki
Department Of Anesthesiology Kyoto Prefectural University Of Medicine
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Hirose Munetaka
Department Of Anesthesiology And Reanimatology Faculty Of Medical Sciences University Of Fukui
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Tanaka Yoshifumi
Department Of Anesthesia Faculty Of Medicine University Of Tokyo
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HIROSE Munetaka
Department of Anesthesia and Pain Clinic, Kusatsu General Hospital
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