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Regulation of δ‐Opioid Receptor mRNA Levels by Receptor‐Mediated and Direct Activation of the Adenylyl Cyclase‐Protein Kinase A Pathway
Author(s) -
Buzas Beata,
Rosenberger John,
Cox Brian M.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68020610.x
Subject(s) - adenylyl cyclase , adcy9 , chemistry , adcy10 , camp dependent pathway , receptor , protein kinase a , microbiology and biotechnology , biology , biochemistry , kinase
The effects of activation of the adenylyl cyclase‐protein kinase A pathway on the expression of δ‐opioid receptor mRNA in the NG108‐15 neuroblastoma × glioma cell line has been investigated. Activation of prostaglandin E 1 (PGE 1 ) receptors, which are positively coupled to adenylyl cyclase, resulted in a reduction in δ‐receptor messenger RNA levels. Direct stimulation of adenylyl cyclase by forskolin or treatment of cells with the cyclic AMP analogue dibutyryl cyclc AMP (db‐cAMP) mimicked the effect of PGE 1 . Down‐regulation in receptor protein levels, as measured by loss of radioligand binding sites, was also observed and its extent correlated well with the decrease in the amount of δ‐opioid receptor transcripts. d ‐Ser 2 ‐Leu‐enkephalin‐Thr 6 (DSLET) inhibition of adenylyl cyclase activity was also diminished after db‐cAMP treatment. Inhibitors of protein kinase A(PKA) partially reversed the PGE 1 ‐and db‐cAMP‐mediated repression of the δ‐opioid receptor mRNA levels. The rate of degradation of δ‐opioid receptor mRNA in the presence of actinomycin D was not altered in response to db‐cAMP, suggesting that mRNA stability is not reduced by PKA action. The regulation of δ‐opioid receptor mRNA levels by db‐cAMP was not sensitive to the protein synthesis inhibitor cycloheximide, suggesting that de novo protein synthesis is not required in this process.