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Effects of general anesthetics on P2X4 receptors in a mouse microglial cell line.
MedLine Citation:
PMID:  22664778     Owner:  NLM     Status:  In-Data-Review    
The purinergic P2X4 receptors (P2X4Rs) of spinal microglia are upregulated after a peripheral nerve injury and play important roles in the pathogenesis of chronic pain. The effects of general anesthetics on chronic pain and the mechanisms are still unclear. The aim of this study is to examine the effects of general anesthetics on microglial P2X4Rs. Currents induced by ATP were recorded by the whole-cell clamp technique using a mouse microglial cell line (MG5). Isoflurane and sevoflurane, ketamine, thiopental, midazolam, and propofol were coapplied with ATP using the U-tube system or added to the external perfusate. ATP-induced two distinct types of current: P2X4R-mediated and P2X7R-mediated currents. P2X4R-mediated currents were identified pharmacologically and isolated. Volatile anesthetics including sevoflurane and isoflurane and intravenous anesthetics including thiopental, ketamine, and midazolam had no effect at clinically relevant concentrations (n=5-8). Propofol showed a dual effect, potentiating at lower concentrations (0.3-3 µM) and inhibiting at higher concentrations (IC50 57 µM). The maximum enhancement was observed at 1 µM propofol (143±5% of control, n=5). Propofol (1 µM) shifted the dose-response curve for the P2X4R currents to lower concentrations of ATP and increased the maximum amplitude. Propofol exerted dual actions on P2X4R-mediated currents at clinically relevant concentrations. This may suggest that the administration of propofol could affect the development of chronic pain through the modulation of microglial P2X4R responses.
Megumi Hasaka; Takashi Mori; Tadashi Matsuura; Toshio Narahashi; Miyuki Kuno; Akira Asada; Kiyonobu Nishikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroreport     Volume:  23     ISSN:  1473-558X     ISO Abbreviation:  Neuroreport     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100935     Medline TA:  Neuroreport     Country:  England    
Other Details:
Languages:  eng     Pagination:  601-5     Citation Subset:  IM    
Departments of aAnesthesiology bPhysiology, Osaka City University Graduate School of Medicine, Osaka, Japan cDepartment of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
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