Modulation of the NO/CO-cGMP signaling cascade during chronic morphine exposure in mice

Neuroscience Letters
De-Yong Liang, J D Clark

Abstract

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.

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Citations

Feb 13, 2010·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Edoardo StagniFilippo Drago
Feb 14, 2009·Pharmacogenetics and Genomics·Larry F ChuJ David Clark
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Aug 14, 2012·International Journal of Nephrology and Renovascular Disease·Marc L WeberKalpna Gupta
Aug 20, 2014·Oxidative Medicine and Cellular Longevity·Jorge Muñoz-Sánchez, María Elena Chánez-Cárdenas
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Dec 24, 2008·Anesthesiology·Noboru TodaHiroshi Toda
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Sep 3, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Sylvia FittingKurt F Hauser
Jan 18, 2017·Oxidative Medicine and Cellular Longevity·Nicholas AsiimweNa Young Jeong
Jun 15, 2021·European Journal of Pharmacology·Renata WolińskaMagdalena Bujalska-Zadrożny
Sep 27, 2005·Biochemical and Biophysical Research Communications·Mahin D Maines, Peter E M Gibbs
Nov 20, 2008·Archives of Biochemistry and Biophysics·Daniela Salvemini

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