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Am J Physiol Endocrinol Metab 254: E54-E62, 1988;
0193-1849/88 $5.00
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AJP - Endocrinology and Metabolism, Vol 254, Issue 1 E54-E62, Copyright © 1988 by American Physiological Society

ARTICLES

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

M. S. Katz
Department of Medicine, University of Texas Health Science Center, San Antonio.

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.


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