β-Adrenergic and Muscarinic Receptor Expression are Regulated in Opposite Ways During Senescence in Rat Left Ventricle

Abstract The well-known attenuated sensitivity of senescent heart to isoproterenol is accompanied by a decreased β 1 -adrenergic receptors ( β 1 -AR) density, a downregualtion process which may involve several molecular modifications and whose understanding is uncomplete. Data concerning the M 2 -R muscarinic receptors (M 2 -R) are more contradictory. Both the absolute and relative concentrations of β 1 -AR and M 2 -R as well as the coupling protein G α s and G α i2 mRNAs were determined by slot-blot analysis in the left ventricles (LVs) of 6–7 week and 22-month-old male Wistar rats. In addition, the β -AR and M 2 -R densities were quantitated by radioactive ligand binding. (1) The M 2 -R mRNA concentration increases by 92±32% in senescent as compared to adult animals; by contrast, the density in M 2 -R remains unchanged, suggesting that the M 2 -R expression was not exclusively regulated at a pre-translational level. (2) The β 1-AR mRNA concentration was nearly halved (reduced by 46±9.5%) and paralleled the 51±5.6% diminution of the β -AR density which resulted exclusively from the decrease of β 1 -AR density without change in the β 2 -AR concentration, suggesting a pre-translational regulation of the β 1 -AR expression. (3) G α i2 mRNA concentration was unchanged, while G α s mRNA concentration was reduced by 26±4.6% in senescent compared with adult LVs. To conclude, the different components of the adrenergic and muscarinic systems are differentially regulated during aging.