Effect of Synthetic Cell-Penetrating Peptides on TrkA Activity in PC12 Cells

Journal of Pharmacological Sciences

Kyoko Kageyama¹  Mineo Abe³  Yoshifumi Tanaka¹  Koyo Ueda²  Masahiro Sakaguchi¹  Keita Fukazawa¹  Masayuki Shibazaki¹  Munetaka Hirose²  Kenji Shigemi²  Yoshihiro Kuroda⁴  Fumihiro Shimizu¹  Eri Murata²  Masashi Hirata¹  Mayumi Takatori¹  Tetsuro Isada² 

[1] Department of Anesthesiology, Kyoto Prefectural University of Medicine, Japan;Department of Anesthesiology and Reanimatology, Faculty of Medical Sciences, Fukui University, Japan;Graduate School of Pharmaceutical Sciences, Kyoto University, Japan;Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Japan

关键词: cell-penetrating peptide;    nerve growth factor (NGF);    Tat;    TrkA;    tyrosine phosphorylation;   

DOI  :  10.1254/jphs.FPZ070263

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(22)Cited-By(12)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.

【 授权许可】

Unknown