[Development- and age-related alterations of beta-adrenergic receptor--adenylate cyclase system in rat myocardium]

It is well known that myocardial responsiveness to catecholamines declines with age besides the elevation of plasma catecholamine concentration. Moreover, age-related alterations in beta-adrenergic receptor-adenylate cyclase system are thought to be a mechanism of the decreased responsiveness. In this study, using Wistar rat myocardium (3, 26, 52, 104 weeks old), alterations in beta-adrenergic receptor (Rs), stimulatory guanine nucleotide-binding protein (Gs), inhibitory guanine nucleotide-binding protein (Gi), and catalytic unit of adenylate cyclase system (C) were investigated. All components consisting the system altered with development and aging: 1) The density of Rs (Bmax) decreased with development. On the other hand, the dissociation constant of Rs (Kd) to Iodocyanopindolol did not change. 2) Forskolin-stimulated activity of C decreased significantly between 3 and 26, between 52 and 104 weeks old. 3) Activity of Gs decreased with development, and did not with aging. In addition, SDS-PAGE and autoradiography revealed that the major alpha-subunits of Gs ADP-ribosylated by cholera toxin changed from peptides of Mr = 45,000 and 47,000 to peptide of Mr = 52,000 with aging. 4) The function of G1 declined with aging. And it was confirmed in this study that function of G1 declined with aging. And it was confirmed in this study that alpha-subunit of Gi ADP -ribosylated by IAP (islet-activating protein) decreased with development and aging.