RGD Reference Report - Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes. - Rat Genome Database

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Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes.

Authors: Rau, Thomas  Nose, Monika  Remmers, Ute  Weil, Joachim  Weissmüller, Astrid  Davia, Kerry  Harding, Sian  Peppel, Karsten  Koch, Walter J  Eschenhagen, Thomas 
Citation: Rau T, etal., FASEB J. 2003 Mar;17(3):523-5. doi: 10.1096/fj.02-0660fje. Epub 2003 Jan 21.
RGD ID: 13508593
Pubmed: PMID:12631586   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.02-0660fje   (Journal Full-text)

The role of Galpha(i)-2 overexpression in desensitization of beta-adrenergic signaling in heart failure is controversial. An adenovirus-based approach was used to investigate whether overexpression of Galpha(i)-2 impairs beta-adrenergic stimulation of adenylyl cyclase (AC) activity and cAMP levels in neonatal rat cardiac myocytes (NRCM) and cell shortening of adult rat ventricular myocytes (ARVM). Infection of NRCM with Ad5Galpha(i)-2 increased Galpha(i)-2 by 50-600% in a virus dose-dependent manner. Overexpression was paralleled by suppression of GTP- and isoprenaline-stimulated AC by 10-72% (P<0.001) in a PTX-sensitive manner. Isoprenaline-stimulated shortening of Ad5Galpha(i)-2-infected ARVM was attenuated by 34% (P<0.01). Ad5Galpha(i)-2/GFP (Galpha(i)-2, green fluorescent protein; bicistronic) was constructed to monitor transfection homogeneity and target Galpha(i)-2 overexpression to levels found in heart failure. At Galpha(i)-2 levels of 93% above control, isoprenaline-stimulated AC activity and cAMP levels were reduced by 17% and 40% (P<0.02), respectively. Beta1- and beta2-adrenergic stimulation was reduced similarly. Our results suggest that (a) the Galpha(i)-2 system exhibits tonic inhibition of stimulated AC in cardiac myocytes, (b) Galpha(i)-2-mediated inhibition is concentration-dependent and occurs at Galpha(i)-2 levels seen in heart failure, and (c) Galpha(i)-2-mediated inhibition affects both beta1- and beta2-adrenergic stimulation of AC. The data argue for an important, independent role of the Galpha(i)-2 increase in heart failure.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway  IDA 13508593 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gnai2  (G protein subunit alpha i2)


Additional Information