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The effect of age on adenosine A1 receptor function in the rat heart
Journal article   Peer reviewed

The effect of age on adenosine A1 receptor function in the rat heart

E Gao, D L Snyder, M D Johnson, E Friedman, J Roberts and J Horwitz
Journal of molecular and cellular cardiology, v 29(2), pp 593-602
Feb 1997
DOI: https://doi.org/10.1006/jmcc.1996.0302
PMID: 9140818
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Theophylline - analogs & derivatives Age Factors Muscarinic Agonists - pharmacology Rats, Inbred F344 Male Adenylyl Cyclases - drug effects Adenylyl Cyclase Inhibitors Myocardium - metabolism Sulfonic Acids Cell Membrane - metabolism Purinergic P1 Receptor Agonists Cell Membrane - drug effects Colforsin - pharmacology Adrenergic beta-Agonists - pharmacology Rats Receptors, Purinergic P1 - physiology Adenosine - pharmacology Adenylyl Cyclases - metabolism Cardiovascular Agents - pharmacology Carbachol - pharmacology Animals Adenosine - analogs & derivatives Isoproterenol - pharmacology Heart - drug effects Theophylline - pharmacology Receptors, Purinergic P1 - drug effects
Adenosine is an important regulatory metabolite in the heart where it has a cardioprotective function. In the ventricle, the cardioprotective action of adenosine is mediated through the adenosine A1 receptor and inhibition of adenylyl cyclase. In order to investigate the effect of age on adenosine signal transduction in the heart, the effect of specific adenosine A receptor agonists on adenylyl cyclase activity was measured in crude cardiac ventricular membranes isolated from 1-, 6- and 24-month-old Fisher 344 rats. There were no differences in basal cyclase activity with age. Consistent with observations from other laboratories, isoproterenol- and forskolin-stimulated cyclase activity decreased with age. In addition, there was an age-related decline in the capacity of adenosine to inhibit stimulated adenylyl cyclase. The specific A1 adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and N6-p-sulfophenuladenosine (SPA) inhibited isoproterenol- and forskolin-stimulated adenylyl cyclase activity in cardiac membranes from 1-month and 6-month-old rats; however, CPA and SPA did not inhibit adenylyl cyclase in membranes from 24-month-old rats. These data indicate that in addition to the age-related decline in beta-adrenergic receptor function with age, there is also a decrease in adenosine A; receptor-mediated responses. In contrast, carbachol acting through muscarinic receptors, caused the same inhibition of adenylyl cyclase at all ages. Therefore, the age-related decline in inhibitory signal transduction is specific to the adenosine A1 receptor. The age-related defect is probably at the level of the adenosine/receptor interaction and/or the receptor/guanine nucleotide binding protein interaction.

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Web of Science research areas
Cardiac & Cardiovascular Systems
Cell Biology
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