Opioid tolerance/dependence in neuroblastoma×glioma (NG108‐15) hybrid cells is associated with a reduction in spontaneous stimulatory receptor activity

FEBS Letters

Schulz, Rüdiger¹  Ammer, Hermann¹ 

[1] Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Königinstrasse 16, D-80539 Munich, Germany

关键词: β2-Adrenoceptor;    Precoupling;    Opioid dependence;    Inverse agonist;    AC;    adenylyl cyclase;    β2-AR;    β2-adrenoceptor;    CYP;    cyanopindolol;    G protein;    guanine nucleotide-binding protein;    Gs;    stimulatory G protein;    Gsα;    α-subunit of Gs;    ICI-118;    551;    (±)-1-[2;    3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyl-ethyl)amino]-2-butanol hydrochloride;    OR;    opioid receptor;   

DOI  :  10.1016/S0014-5793(00)02207-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Chronic opioid regulation of stimulatory receptor activity was investigated in neuroblastoma×glioma (NG108-15) hybrid cells stably transfected to express the human β₂-adrenoceptor (β₂-AR). Expressed β₂-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 β₂-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.

【 授权许可】

Unknown