Document Detail


Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A.
MedLine Citation:
PMID:  17897634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effects of morphine and other agonists on the human mu opioid receptor (MOP) expressed in M2 melanoma cells, lacking the actin cytoskeleton protein filamin A and in A7, a subclone of the M2 melanoma cells, stably transfected with filamin A cDNA. The results of binding experiments showed that after chronic morphine treatment (24 h) of A7 cells, MOP-binding sites were down-regulated to 63% of control, whereas, unexpectedly, in M2 cells, MOP binding was up-regulated to 188% of control naive cells. Similar up-regulation was observed with the agonists methadone and levorphanol. The presence of antagonists (naloxone or CTAP) during chronic morphine treatment inhibited MOP down-regulation in A7 cells. In contrast, morphine-induced up-regulation of MOP in M2 cells was further increased by these antagonists. Chronic morphine desensitized MOP in A7 cells, i.e., it decreased DAMGO-induced stimulation of GTPgammaS binding. In M2 cells DAMGO stimulation of GTPgammaS binding was significantly greater than in A7 cells and was not desensitized by chronic morphine. Pertussis toxin treatment abolished morphine-induced receptor up-regulation in M2 cells, whereas it had no effect on morphine-induced down-regulation in A7 cells. These results indicate that, in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of MOP, to our knowledge, the first instance of opioid receptor up-regulation by agonists in cell culture.
Authors:
Irma Onoprishvili; Eric J Simon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-08-16
Journal Detail:
Title:  Brain research     Volume:  1177     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-19     Completed Date:  2008-01-15     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  9-18     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Cell Line
Cell Line, Tumor
Contractile Proteins / deficiency,  physiology*
Data Interpretation, Statistical
Diprenorphine / pharmacology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Humans
Ligands
Melanoma / genetics,  pathology
Microfilament Proteins / deficiency,  physiology*
Morphine / pharmacology*
Narcotic Antagonists / metabolism,  pharmacology
Narcotics / pharmacology*
Pertussis Toxin / pharmacology
Radioligand Assay
Receptors, Opioid, mu / agonists,  drug effects*,  metabolism
Tubulin / pharmacology
Up-Regulation / drug effects
Grant Support
ID/Acronym/Agency:
DA-072545/DA/NIDA NIH HHS; DA00017/DA/NIDA NIH HHS; R01 DA000017-40S2/DA/NIDA NIH HHS; T32 DA007254-15/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Contractile Proteins; 0/Ligands; 0/Microfilament Proteins; 0/Narcotic Antagonists; 0/Narcotics; 0/Receptors, Opioid, mu; 0/Tubulin; 0/filamins; 100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; 14357-78-9/Diprenorphine; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 57-27-2/Morphine; EC 2.4.2.31/Pertussis Toxin
Comments/Corrections

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