Effect of age on beta-receptors, Gs alpha- and Gi alpha- proteins in rat heart

beta-adrenoceptors, Gs alpha- and Gi alpha-proteins were investigated in a crude plasma membrane preparation from ventricles of young (2-4 months) and senescent (22-24 months) Wistar rats. Receptor density, ligand affinity and beta 1/beta 2-receptor ratio were independent of the age of the rats. The percentage of beta-receptors coupled to G-proteins increased with age. An age-related increase in the level of Gs alpha (124%) was paralleled by an increase in the ratio between the high and low molecular weight form of Gs alpha. The level of Gi alpha-protein almost doubled (170%) upon aging. We conclude that the age-related differences are small at the level of the beta-adrenoceptor molecule, but that the increase in Gi alpha-proteins could be responsible for the age-related reduction in myocardial inotropic and chronotropic responses. Moreover, we suggest that the changes in degree of high affinity coupling between beta-receptor and Gs-protein are possibly linked to alterations in the ratio between the Gs-molecular weight subtypes.