Chronic morphine-mediated adenylyl cyclase superactivation is attenuated by the Raf-1 inhibitor, GW5074

Xu Yue, Eva V. Varga, Dagmar Stropova, Todd W Vanderah, Henry I. Yamamura, William R Roeske

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The utility of morphine for the treatment of chronic pain is limited by the development of analgesic tolerance. Adenylyl cyclase (AC) superactivation, induced by chronic opioid agonist administration, is regarded as one of the molecular mechanisms leading to tolerance. In the present work, we tested the role of Raf-1 in morphine-mediated AC superactivation in CHO cells stably expressing the human μ-opioid receptor. We found that pretreatment of CHO cells stably expressing the human μ-opioid receptor with the selective Raf-1 inhibitor, 3-(3,5-dibromo-4-hydroxybenzylidene)-5-iodo-1,3-dihydroindol-2-one (GW5074, 10 μM, 60 min) completely abolished chronic morphine-mediated AC superactivation (P < 0.01). This finding indicates that Raf-1 may have a crucial role in compensatory feedback regulation of cellular cAMP levels by clinically important opioid analgesics.

Original languageEnglish (US)
Pages (from-to)57-59
Number of pages3
JournalEuropean Journal of Pharmacology
Volume540
Issue number1-3
DOIs
StatePublished - Jul 1 2006

Fingerprint

Adenylyl Cyclases
Morphine
CHO Cells
Opioid Receptors
Opioid Analgesics
Chronic Pain
Analgesics
5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone
Therapeutics

Keywords

  • Adenylyl cyclase superactivation
  • Human μ-opioid receptor
  • Raf-1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Chronic morphine-mediated adenylyl cyclase superactivation is attenuated by the Raf-1 inhibitor, GW5074. / Yue, Xu; Varga, Eva V.; Stropova, Dagmar; Vanderah, Todd W; Yamamura, Henry I.; Roeske, William R.

In: European Journal of Pharmacology, Vol. 540, No. 1-3, 01.07.2006, p. 57-59.

Research output: Contribution to journalArticle

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AU - Roeske, William R

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