Food restriction modulates beta-adrenergic-sensitive adenylate cyclase in rat liver during aging

Adenylate cyclase activities were studied in rat liver during post-maturational aging of male Fischer 344 rats fed ad libitum or restricted to 60% of the ad libitum intake. Catecholamine (10(-5) M epinephrine, isoproterenol, or norepinephrine)-stimulated adenylate cyclase activity increased by 200-300% between 6 and 24-27 mo of age in ad libitum-fed rats, whereas in food-restricted rats catecholamine response increased by only 58-84% between 6 and 30 mo. In ad libitum-fed rats, glucagon (10(-5) M)-stimulated enzyme activity also increased by 40% between 6 and 12 mo and in restricted rats a similar age-related increase was delayed until 18 mo. beta-Adrenergic receptor density (Bmax, determined from saturation binding of the beta-adrenergic antagonist l-[125I]iodopindolol) increased by 50% between 6 and 24 mo in livers from ad libitum-fed but not food-restricted rats and showed a highly significant correlation with maximal isoproterenol-stimulated adenylate cyclase activity over the post-maturational life span. Age-related increases in unstimulated (basal) adenylate cyclase activity and nonreceptor-mediated enzyme activation (by guanine nucleotides, fluoride, and to a lesser extent forskolin) were retarded by food restriction. The results demonstrate that food restriction diminishes a marked age-related increase in beta-adrenergic-sensitive adenylate cyclase activity of rat liver. Alterations of adrenergic-responsive adenylate cyclase with age and the modulatory effects of food restriction appear to be mediated by changes in both receptor and nonreceptor components of adenylate cyclase.