Altered subcellular signaling in murine peritoneal macrophages upon chronic morphine exposure

J Neuroimmunol. 2006 Jul;176(1-2):86-94. doi: 10.1016/j.jneuroim.2006.04.007. Epub 2006 Jun 5.


Alterations in opioid signaling that take place in murine peritoneal macrophages in vitro are variably dependent on opiate exposure conditions. Acute exposure to morphine inhibits Fc-mediated phagocytosis by a pertussis toxin (PT)-sensitive mechanism, but has no effect on cAMP levels. In contrast, chronic exposure to morphine results in a "tolerant" state, wherein test and control values for both phagocytosis and cAMP are equivalent. However, drug withdrawal after chronic exposure to morphine results in inhibition of phagocytosis and a concomitant 4-fold increase in cAMP by a PT-insensitive mechanism. This increase is causally related to inhibition of phagocytosis since an artificial increase in cAMP inhibits phagocytosis in non-withdrawn cells exposed chronically to morphine. We suggest that macrophage opioid receptors signaling switches from a Gi/o-mediated mechanism that does not involve adenylate cyclase in acute exposure to a non-Gi/o-mediated adenylate cyclase superactivation during chronic exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Cyclic AMP / analysis
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Female
  • Macrophages, Peritoneal / immunology*
  • Mice
  • Mice, Inbred C3H
  • Morphine / pharmacology*
  • Pertussis Toxin / pharmacology
  • Phagocytosis / drug effects
  • Signal Transduction / drug effects*


  • Morphine
  • Cyclic AMP
  • Pertussis Toxin
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases