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

The well-known attenuated sensitivity of senescent heart to isoproterenol is accompanied by a decreasedβ1-adrenergic receptors (β1-AR) density, a downregualtion process which may involve several molecular modifications and whose understanding is uncomplete. Data concerning the M2-R muscarinic receptors (M2-R) are more contradictory. Both the absolute and relative concentrations ofβ1-AR and M2-R as well as the coupling protein Gαs and Gαi2mRNAs were determined by slot-blot analysis in the left ventricles (LVs) of 6–7 week and 22-month-old male Wistar rats. In addition, theβ-AR and M2-R densities were quantitated by radioactive ligand binding. (1) The M2-R mRNA concentration increases by 92±32% in senescent as compared to adult animals; by contrast, the density in M2-R remains unchanged, suggesting that the M2-R expression was not exclusively regulated at a pre-translational level. (2) Theβ1-AR mRNA concentration was nearly halved (reduced by 46±9.5%) and paralleled the 51±5.6% diminution of theβ-AR density which resulted exclusively from the decrease ofβ1-AR density without change in theβ2-AR concentration, suggesting a pre-translational regulation of theβ1-AR expression. (3) Gαi2mRNA concentration was unchanged, while Gαs 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.