Document Detail

Modulation of the NO/CO-cGMP signaling cascade during chronic morphine exposure in mice.
MedLine Citation:
PMID:  15234476     Owner:  NLM     Status:  MEDLINE    
The chronic administration of morphine and related opioid drugs results in tolerance and dependence which reduces the clinical utility of these agents. The CO/NO-cGMP signal transduction cascade plays an important role in morphine tolerance. Principal components of this pathway include heme oxygenase (HO), nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and cyclic GMP-dependent protein kinase (cGK). We measured and compared the spinal gene expression patterns of these key components using real-time PCR and Western blot analysis after chronic morphine treatment in mice. Our findings indicate that the CO/NO-cGMP signaling pathway is upregulated at multiple points after morphine exposure demonstrating a coordinated molecular and biochemical response. These findings underscore the importance of this signaling pathway in the neuroplastic events occurring during chronic opioid exposure and the value of analyzing the participation of multiple components of a signaling pathway simultaneously rather than individual members in isolation.
De-Yong Liang; J David Clark
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Neuroscience letters     Volume:  365     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-05     Completed Date:  2004-09-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  73-7     Citation Subset:  IM    
Department of Anesthesiology, Stanford University and Veterans Affairs Palo Alto Health Care System, 112A, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
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MeSH Terms
Blotting, Western
Carbon Monoxide / metabolism
Cyclic GMP / metabolism
Cyclic GMP-Dependent Protein Kinases / biosynthesis
Drug Tolerance / physiology*
Electrophoresis, Polyacrylamide Gel
Gene Expression
Guanylate Cyclase
Heme Oxygenase (Decyclizing) / biosynthesis
Morphine / pharmacology*
Narcotics / pharmacology*
Nitric Oxide / metabolism
Nitric Oxide Synthase / biosynthesis
Receptors, Cytoplasmic and Nuclear / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects*,  physiology
Spinal Cord / enzymology
Time Factors
Reg. No./Substance:
0/Narcotics; 0/Receptors, Cytoplasmic and Nuclear; 10102-43-9/Nitric Oxide; 57-27-2/Morphine; 630-08-0/Carbon Monoxide; 7665-99-8/Cyclic GMP; EC Oxide Synthase; EC Oxygenase (Decyclizing); EC GMP-Dependent Protein Kinases; EC Cyclase; EC guanylyl cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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