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Endocrinology, Vol 120, 1534-1541, Copyright © 1987 by Endocrine Society


ARTICLES

Beta-adrenergic receptors, glucagon receptors, and their relationship to adenylate cyclase in rat liver during aging

EM Dax, JS Partilla, MA Pineyro and RI Gregerman

The beta-adrenergic and glucagon receptor-binding capacities in rat livers from 6-27 months of age were measured to investigate the mechanism of a previously observed rise in beta-adrenergic stimulated adenylate cyclase with increasing age. There was no concomitant increase in glucagon-stimulated adenylate cyclase. In the present study neither glucagon-binding capacity nor glucagon-stimulated adenylate cyclase changed with age. In contrast, the beta-adrenergic receptor capacity, measured in the same membranes by [125I]iodopindolol binding, increased nearly 3-fold from 6.6 +/- 0.6 fmol/mg at 6 months to 19.1 +/- 3.3 fmol/mg at 18-19 months. The increase was directly proportional to the maximum isoproterenol-stimulated adenylate cyclase activity in livers of rats up to 19 months of age. By 24-27 months the binding capacity had increased to 24.9 +/- 3.3 fmol/mg, but there was no further increase in adenylate cyclase activity. Thus, there appeared to be a beta-receptor-adenylate cyclase uncoupling in livers from the senescent animals (25-27 months). The defect could not be demonstrated by studies examining isoproterenol competition of [125I]iodopindolol from agonist-induced high affinity sites on the membranes, a procedure that examines receptor-Ns protein coupling. Activation of adenylate cyclase by the nonhormonal stimulators F- and forskolin did not change with age, indicating that the catalytic unit was not a limiting factor. Since the relationship between the glucagon receptor and adenylate cyclase also remained unaltered, the uncoupling apparently lies in an alteration of the interaction between the beta-adrenergic receptor and the guanine nucleotide-sensitive Ns protein.


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Am. J. Physiol. Endocrinol. Metab.Home page
D. A. Podolin, B. K. Wills, I. O. Wood, M. Lopez, R. S. Mazzeo, and D. A. Roth
Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training
Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E516 - E523.
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