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

21 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Chronic morphine-mediated adenylyl cyclase superactivation is attenuated by the Raf-1 inhibitor, GW5074'. Together they form a unique fingerprint.

  • Cite this