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.
Bazan
A
A
Heymans Institute of Pharmacology, University of Ghent, Medical School, Belgium.
Van de Velde
E
E
Fraeyman
N
N
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D007106:Immune Sera / Q000276:immunology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D007106:Immune Sera; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol