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Opioid tolerance/dependence in neuroblastoma×glioma (NG108‐15) hybrid cells is associated with a reduction in spontaneous stimulatory receptor activity
Author(s) -
Ammer Hermann,
Schulz Rüdiger
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02207-9
Subject(s) - adenylyl cyclase , neuroblastoma , receptor , basal (medicine) , endocrinology , inverse agonist , chemistry , medicine , agonist , opioid , g protein , opioid receptor , transfection , biology , cell culture , biochemistry , gene , genetics , insulin
Chronic opioid regulation of stimulatory receptor activity was investigated in neuroblastoma×glioma (NG108‐15) hybrid cells stably transfected to express the human β 2 ‐adrenoceptor (β 2 ‐AR). Expressed β 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 β 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.