RGD Reference Report - Modulation of adrenal catecholamine secretion by in vivo gene transfer and manipulation of G protein-coupled receptor kinase-2 activity. - Rat Genome Database

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Modulation of adrenal catecholamine secretion by in vivo gene transfer and manipulation of G protein-coupled receptor kinase-2 activity.

Authors: Lymperopoulos, A  Rengo, G  Zincarelli, C  Soltys, S  Koch, WJ 
Citation: Lymperopoulos A, etal., Mol Ther. 2008 Feb;16(2):302-7. doi: 10.1038/sj.mt.6300371. Epub 2007 Nov 27.
RGD ID: 8553863
Pubmed: PMID:18223549   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.mt.6300371   (Journal Full-text)

We recently reported that the upregulation of adrenal G protein-coupled receptor kinase-2 (GRK2) causes enhanced catecholamine (CA) secretion by desensitizing sympatho-inhibitory alpha (2)-adrenergic receptors (alpha (2)ARs) of chromaffin cells, and thereby aggravating heart failure (HF). In this study, we sought to develop an efficient and reproducible in vivo adrenal gene transfer method to determine whether manipulation of adrenal GRK2 levels/activity regulates physiological CA secretion in rats. We specifically investigated two different in vivo gene delivery methods: direct injection into the suprarenal glands, and retrograde delivery through the suprarenal veins. We delivered adenoviral (Ad) vectors containing either GRK2 or an inhibitor of GRK2 activity, the beta ARKct. We found both delivery approaches equally effective at supporting robust (>80% of the whole organ) and adrenal-restricted transgene expression, in the cortical region as well as in the medullar region. Additionally, rats with AdGRK2-infected adrenals exhibit enhanced plasma CA levels when compared with control rats (AdGFP-injected adrenals), whereas plasma CA levels after Ad beta ARKct infection were significantly lower. Finally, in isolated chromaffin cells, alpha (2)ARs of AdGRK2-infected cells failed to inhibit CA secretion whereas Ad beta ARKct-infected cells showed normal alpha (2)AR responsiveness. These results not only indicate that in vivo adrenal gene transfer is an effective way of manipulating adrenal gland signalling, but also identify GRK2 as a critically important molecule involved in CA secretion.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grk2Ratdesensitization of G protein-coupled receptor signaling pathway involved_inIDA PMID:18223549BHF-UCL 
Grk2Ratpositive regulation of catecholamine secretion involved_inIDA PMID:18223549BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Grk2  (G protein-coupled receptor kinase 2)


Additional Information