title: Decrease in beta 1-adrenergic and M2-muscarinic receptor mRNA levels and unchanged accumulation of mRNAs coding for G alpha i-2 and G alpha s proteins in rat cardiac hypertrophy.
abstract: During compensatory cardiac hypertrophy in the rat, hemodynamic overload induces a parallel decrease in the densities of both beta 1-adrenergic (beta 1-AR) and M2-muscarinic (M2-MR) receptors in the left ventricle, but the total number of receptors remains unchanged. It is not known whether this reduction is transcriptionally or translationally regulated, or if the functionally closely linked alpha-subunits of G protein (G alpha s and G alpha i-2) partake in this regulation. In order to resolve these questions, the absolute concentrations of mRNAs for both receptors and for G alpha s and G alpha i-2 were quantified by slot blot analysis of the left ventricles of adult rats 5 weeks after aortic banding. The results showed a significant decrease of both receptor mRNA levels in hypertrophied left ventricle (beta 1-AR: -48%; M2-MR: -42%) that paralleled the reduction in receptor protein densities and was negatively correlated with the left ventricular weight/body weight ratio (LVW/BW). By contrast, the relative levels of G alpha s and G alpha i-2 mRNAs remained unchanged, and both accumulated proportionally to the increase in LVW/BW. These results show that the beta 1-AR and the M2-MR were pretranslationally regulated. This suggests the hypothesis that the corresponding genes do not follow the general increase in transcriptional activity. By contrast, the genes coding for G alpha s and G alpha i-2 may follow the general pattern of activation during hypertrophy. Receptors and coupling proteins belong to two different groups of genes that are controlled by distinct mechanisms of regulation.
authors.affiliation: INSERM U127, IFR Circulation Lariboisière, Université D. Diderot, Hôpital Lariboisière, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Mondry
authors.forename: F
authors.initials: F
authors.lastname: Bourgeois
authors.forename: F
authors.initials: F
authors.lastname: Carré
authors.forename: B
authors.initials: B
authors.lastname: Swynghedauw
authors.forename: J M
authors.initials: JM
authors.lastname: Moalic
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal; D001835:Body Weight; D003250:Constriction; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins