RT Journal Article
SR Electronic
T1 Age-Related Decline in <em>Beta</em> Adrenergic and Adenosine A<sub>1</sub> Receptor Function in the Heart Are Attenuated by Dietary Restriction
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 186
OP 192
VO 285
IS 1
A1 Erhe Gao
A1 David L. Snyder
A1 Jay Roberts
A1 Eitan Friedman
A1 Guoping Cai
A1 Amir Pelleg
A1 Joel Horwitz
YR 1998
UL http://jpet.aspetjournals.org/content/285/1/186.abstract
AB Previously published reports from this laboratory have shown that the antiadrenergic effect of adenosine A1 agonists declines with age in the rat heart [Gao et al. (1997)J Mol Cell Cardiol 29:593–602] and that this decline may be caused by a decrease in coupling between adenosine A1 receptors (AdoA1R) and guanine nucleotide-binding proteins [Cai et al. (1997)Circ Res 81:1065–1071]. Dietary restriction (DR; 60% calories of ad libitum) has been shown to attenuate age-related changes in cellular signal transduction pathways. Therefore, the present study investigated whether DR altered the age-related changes in AdoA1R-mediated function in senescent rat hearts. Ventricular membranes were isolated from the hearts of ad libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In AL rats, there was an age-related decline in isoproterenol (ISO)-stimulated adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO-stimulated cyclase was attenuated in DR animals. In AL rats, inhibition of ISO-stimulated adenylyl cyclase by the AdoA1R agonist, N6-p-sulfophenyladenosine (SPA) decreased with age. In DR rats, the age-related decline in inhibition was attenuated. Previous results from this laboratory indicated that in AL fed rats, there was an age-related decrease in the percentage of high-affinity binding sites for SPA, from 55% at 6 months to 23% at 24 months. Diet restriction attenuated this age-related shift in high-affinity binding sites so that the percentage of high-affinity sites at 24 months was 42%. Our results suggest that DR maintains AdoA1R function by preventing a loss of high-affinity AdoA1R sites. The American Society for Pharmacology and Experimental Therapeutics