Opioid tolerance/dependence in neuroblastoma x glioma (NG108-15) hybrid cells is associated with a reduction in spontaneous stimulatory receptor activity.
Chronic opioid regulation of stimulatory receptor activity was investigated in neuroblastoma x glioma (NG108-15) hybrid cells stably transfected to express the human beta(2)-adrenoceptor (beta(2)-AR). Expressed beta(2)-ARs are functionally coupled to G proteins and display ligand-independent signalling activity, as demonstrated by the ability of an inverse agonist to attenuate basal adenylyl cyclase (AC) activity. Despite the relative increase in basal AC activity due to the development of tolerance/dependence, chronic morphine treatment was found to completely abolish spontaneous beta(2)-AR activity by reducing basal receptor/G protein precoupling. A similar chronic opioid effect was observed in transiently transfected COS-7 cells. These results indicate that during the state of opioid tolerance/dependence basal levels of AC activity are no longer under the control of spontaneously active stimulatory receptors.
Ammer
H
H
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Königinstrasse 16, D-80539 Munich, Germany. ammer@pharmtox.vetmed.uni-muenchen.de
Schulz
R
R
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D007457:Iodine Radioisotopes; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D009294:Narcotics; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C026777:ICI 118551; C047975:cyanopindolol; D009020:Morphine; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases