RGD Reference Report - Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and beta-arrestin-2 in postmortem brains of opiate addicts. - Rat Genome Database

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Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and beta-arrestin-2 in postmortem brains of opiate addicts.

Authors: Ferrer-Alcón, Marcel  La Harpe, Romano  García-Sevilla, Jesús A 
Citation: Ferrer-Alcón M, etal., Brain Res Mol Brain Res. 2004 Feb 5;121(1-2):114-22. doi: 10.1016/j.molbrainres.2003.11.009.
RGD ID: 401901596
Pubmed: PMID:14969742   (View Abstract at PubMed)
DOI: DOI:10.1016/j.molbrainres.2003.11.009   (Journal Full-text)

The homologous regulation of opioid receptors, through G protein-coupled receptor kinases (GRKs) and beta-arrestins, is an initial step in the complex molecular mechanisms leading to opiate tolerance and dependence. This study was designed to evaluate in parallel the contents of immunolabeled micro-opioid receptors (glycosylated proteins), two representative GRKs (GRK 2 and GRK 6) and beta-arrestin-2 in brains of opiate addicts who had died of an opiate overdose (heroin or methadone). The immunodensities of micro-opioid receptors were decreased (66 kDa protein: 24%, n=24, P<0.0001; 85 kDa protein: 16%, n=24, P<0.05) in the prefrontal cortex of opiate addicts compared with sex-, age-, and PMD-matched controls. This down-regulation of brain micro-opioid receptors was more pronounced in opiate addicts dying of a heroin overdose (27-30%, n=13) than in those who died of a methadone overdose (5-16%, n=11). In the same brains, significant decreases in the immunodensities of GRK 2 (19%, n=24, P<0.05), GRK 6 (25%, n=24, P<0.002) and beta-arrestin-2 (22%, n=24, P< 0.0005) were also quantitated. In contrast, the content of alpha-internexin (a neuronal marker used as a negative control) was not changed in brains of opiate addicts. In these subjects, there was a significant correlation between the densities of GRK 6 and beta-arrestin-2 (r=0.63, n=24, P=0.001), suggesting that both proteins are regulated in a coordinated manner by opiate drugs in the brain. The results indicate that opiate addiction in humans (tolerant state) is associated with down-regulation of brain micro-opioid receptors and regulatory GRK 2/6 and beta-arrestin-2 proteins. These molecular adaptations may be relevant mechanisms for the induction of opiate tolerance in brains of opiate addicts.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARRB2Humanopiate dependence  IEP protein:decreased expression:pre-frontal cortexRGD 
Arrb2Ratopiate dependence  ISOARRB2 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
Arrb2Mouseopiate dependence  ISOARRB2 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
GRK2Humanopiate dependence  IEP protein:decreased expression:pre-frontal cortexRGD 
GRK6Humanopiate dependence  IEP protein:decreased expression:pre-frontal cortexRGD 
Grk2Ratopiate dependence  ISOGRK2 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
Grk2Mouseopiate dependence  ISOGRK2 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
Grk6Ratopiate dependence  ISOGRK6 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
Grk6Mouseopiate dependence  ISOGRK6 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
OPRM1Humanopiate dependence  IEP protein:decreased expression:pre-frontal cortexRGD 
Oprm1Ratopiate dependence  ISOOPRM1 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 
Oprm1Mouseopiate dependence  ISOOPRM1 (Homo sapiens)protein:decreased expression:pre-frontal cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Arrb2  (arrestin, beta 2)
Grk2  (G protein-coupled receptor kinase 2)
Grk6  (G protein-coupled receptor kinase 6)
Oprm1  (opioid receptor, mu 1)

Genes (Mus musculus)
Arrb2  (arrestin, beta 2)
Grk2  (G protein-coupled receptor kinase 2)
Grk6  (G protein-coupled receptor kinase 6)
Oprm1  (opioid receptor, mu 1)

Genes (Homo sapiens)
ARRB2  (arrestin beta 2)
GRK2  (G protein-coupled receptor kinase 2)
GRK6  (G protein-coupled receptor kinase 6)
OPRM1  (opioid receptor mu 1)


Additional Information