title: Altered subcellular signaling in murine peritoneal macrophages upon chronic morphine exposure.
abstract: 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is causally related to inhibition of phagocytosis since an artificial increase in cAMP inhibits phagocytosis in non-withdrawn cells exposed chronically to morphine.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.
authors.affiliation: Department of Natural Sciences, Interamerican University, Bayamón Campus, Bayamón, Puerto Rico.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lugo-Chinchilla
authors.forename: Dennise
authors.initials: D
authors.lastname: Báez
authors.forename: Mariella
authors.initials: M
authors.lastname: Vélez
authors.forename: Cristhian
authors.initials: C
authors.lastname: Ildefonso
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Renaud
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005260:Female; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009020:Morphine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases