DECREASE IN BETA(1)-ADRENERGIC AND M(2)-MUSCARINIC RECEPTOR MESSENGER-RNA LEVELS AND UNCHANGED ACCUMULATION OF MESSENGER-RNAS CODING FOR G(ALPHA-I-2) AND G(ALPHA-S) PROTEINS IN RAT CARDIAC-HYPERTROPHY

During compensatory cardiac hypertrophy in the rat, hemodynamic overlo ad induces a parallel decrease in the densities of both beta(1)-adrene rgic (beta(1)-AR) and M(2)-muscarinic (M(2)-MR) receptors in the left ventricle, but the total number of receptors remains unchanged. It is not known whether this reduction is transcriptionally or translational ly regulated, or if the functionally closely linked a-subunits of G pr otein (G(alpha s) and G(alpha i-2)) partake in this regulation. In ord er to resolve these questions, the absolute concentrations of mRNAs fo r both receptors and for G(alpha s) and G(alpha i-2) were quantified b y slot blot analysis of the left ventricles of adult rats 5 weeks afte r aortic banding. The results showed a significant decrease of both re ceptor mRNA levels in hypertrophied left ventricle (beta(1)-AR: -48%; M(2)-MR: -42%) that paralleled the reduction in receptor protein densi ties and was negatively correlated with the left ventricular weight/bo dy weight ratio (LVW/BW), By contrast, the relative levels of G(alpha s) and G(alpha i-2) mRNAs remained unchanged, and both accumulated pro portionally to the increase in LVW/BW, These results show that the bet a(1)-AR and the M(2)-MR were pretranslationally regulated. This sugges ts the hypothesis that the corresponding genes do not follow the gener al increase in transcriptional activity. By contrast, the genes coding for G(alpha) and G(alpha i-2) may follow the general pattern of activ ation during hypertrophy. Receptors and coupling proteins belong to tw o different groups of genes that are controlled by distinct mechanisms of regulation. (C) 1995 Academic Press Limited