BETA-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 isoprotere nol is accompanied by a decreased beta(1)-adrenergic receptors (beta(1 )-AR) density, a downregulation process which may involve several mole cular modifications and whose understanding is uncomplete. Data concer ning the M(2)-R muscarinic receptors (M(2)-R) are more contradictory. Both the absolute and relative concentrations of beta(1)-AR and M(2)-R as well as the coupling protein G alpha s and G alpha(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 beta-AR and M (2)-R densities were quantitated by radioactive ligand binding. (1) Th e M(2)-R mRNA concentration increases by 92+/-32% in senescent as comp ared to adult animals; by contrast, the density in M(2)-R remains unch anged, suggesting that the M(2)-R expression was not exclusively regul ated at a pre-translational level. (2) The beta 1-AR mRNA concentratio n was nearly halved (reduced by 46+/-9.5%) and paralleled the 51+/-5.6 % diminution of the beta-AR density which resulted exclusively from th e decrease of beta(1)-AR density without change in the beta(2)-AR conc entration, suggesting a pre-translational regulation of the beta(1)-AR expression. (3) G alpha(i2) mRNA concentration was unchanged, while G alpha s mRNA concentration was reduced by 26+/-4.6% in senescent comp ared with adult LVs. To conclude, the different components of the adre nergic and muscarinic systems are differentially regulated during agin g. (C) 1997 Academic Press Limited