Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS)
| Autor: | Tetsuya Abe, Tayo Katano, Yasuharu Sasaki, Seiji Ito, Shinichi Tatsumi, Toshiaki Minami, Hiroyoshi Hidaka, Shinji Matsumura, Tamaki Mabuchi, Masaaki Suzuki |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Central nervous system Pain Protein Serine-Threonine Kinases Pharmacology Substrate Specificity Mice 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine medicine Animals Enzyme Inhibitors Phosphorylation MARCKS Myristoylated Alanine-Rich C Kinase Substrate Rho-associated protein kinase Protein kinase C Pain Measurement Inflammation rho-Associated Kinases Dose-Response Relationship Drug biology Chemistry Kinase General Neuroscience Intracellular Signaling Peptides and Proteins Membrane Proteins Nitric oxide synthase medicine.anatomical_structure Biochemistry Neuropathic pain biology.protein |
| Zdroj: | Neuroscience. 131:491-498 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2004.10.022 |
| Popis: | Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser159-phospho-MARCKS (pS159-Mar-Ab) revealed that MARCKS is phosphorylated at Ser159 by Rho-kinase and that its phosphorylation is inhibited by the Rho-kinase specific inhibitor H-1152. Since the function of MARCKS is regulated by phosphorylation at multiple sites, here we examined the involvement of Rho-kinase in relation to phosphorylation of MARCKS at Ser159 in inflammatory and neuropathic pain by H-1152. When intrathecally administered 10 min before s.c. injection of formalin, H-1152 at 10 and 100 ng attenuated the second-phase, but not the first-phase, pain-like behaviors in the formalin test. Neuropathic pain induced by selective L5 spinal nerve transection was also relieved by intrathecal injection of H-1152. Nitric oxide synthase activity visualized by NADPH diaphorase histochemistry increased in the superficial layer of the spinal cord 30 min after formalin injection and 7 days after nerve transection, which were blocked by H-1152. Phosphorylation of MARCKS at Ser159 was detected in the spinal cord by pS159-Mar-Ab and the level of phosphorylation increased in the superficial layer after nerve transection. In contrast, immunoreactivities of neuronal nitric oxide synthase and MARCKS did not change significantly in the spinal cord before and after nerve transection. Taken together, the present study demonstrates that Rho-kinase is involved in inflammatory pain and the maintenance of neuropathic pain through phosphorylation of MARCKS at Ser159. |
| Databáze: | OpenAIRE |
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