title: Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure.
abstract: In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, FRG.
authors.forename: T
authors.initials: T
authors.lastname: Eschenhagen
authors.forename: U
authors.initials: U
authors.lastname: Mende
authors.forename: M
authors.initials: M
authors.lastname: Nose
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
authors.forename: H
authors.initials: H
authors.lastname: Scholz
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.forename: S
authors.initials: S
authors.lastname: Hirt
authors.forename: V
authors.initials: V
authors.lastname: Döring
authors.forename: P
authors.initials: P
authors.lastname: Kalmár
authors.forename: W
authors.initials: W
authors.lastname: Höppner
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology; D003327:Coronary Disease / Q000235:genetics / Q000503:physiopathology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: D012333:RNA, Messenger; D019204:GTP-Binding Proteins