Document Detail

Involvement of activator protein-1 in transcriptional regulation of the human mu-opioid receptor gene.
MedLine Citation:
PMID:  11901219     Owner:  NLM     Status:  MEDLINE    
mu-Opioid receptors mediate such opioid effects as analgesia, euphoria, and immunomodulation. Gene expression of mu-opioid receptors can be modulated by various substances, including cytokines, hormones, and drugs. Some of these stimuli (e.g., IL-1beta and cocaine) have been shown to activate members of the AP-1 transcription factor family. In addition, transcription of the mu-opioid receptor gene is induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, which in turn is an activator of AP-1 transcription factors. This indicates that signaling pathways involving protein kinase C and activator protein 1 (AP-1) transcription factors are important for the specific expression pattern of the mu-opioid receptor gene. In this report, we show that TPA activates AP-1 as well as the transcription factor nuclear factor kappaB (NFkappaB) in the mu-opioid receptor expressing neuroblastoma cell line SH SY5Y. In transfection experiments performed in these cells, both factors trans-activate expression of reporter gene constructs containing the human mu-opioid receptor gene promoter. By excluding the effects of TPA on NFkappaB with the specific NFkappaB inhibitor sulfasalazine, AP-1 regulatory elements were localized. Two AP-1 elements, which differ in one nucleotide each from the classic AP-1 binding site, were delineated to positions -2388 and -1434 of the promoter. Independent of their orientation, these elements conferred TPA responsiveness on the heterologous thymidine kinase promoter. AP-1 binding to these elements was confirmed using electrophoretic mobility shift and immunoshift assays.
Christine Börner; Volker Höllt; Jürgen Kraus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmacology     Volume:  61     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-19     Completed Date:  2002-04-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  800-5     Citation Subset:  IM    
Department of Pharmacology, University of Magdeburg, Magdeburg, Germany.
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MeSH Terms
Cells, Cultured
Gene Expression Regulation* / drug effects,  physiology
NF-kappa B / metabolism
Promoter Regions, Genetic / drug effects,  physiology
Receptors, Opioid, mu / genetics*
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factor AP-1 / physiology*
Transcription, Genetic / drug effects,  physiology*
Tumor Necrosis Factor-alpha / pharmacology
Reg. No./Substance:
0/NF-kappa B; 0/Receptors, Opioid, mu; 0/Transcription Factor AP-1; 0/Tumor Necrosis Factor-alpha; 16561-29-8/Tetradecanoylphorbol Acetate

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