Journal article
The effect of age on adenosine A1 receptor function in the rat heart
Journal of molecular and cellular cardiology, Vol.29(2), pp.593-602
Feb 1997
PMID: 9140818
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- The effect of age on adenosine A1 receptor function in the rat heart
- Creators
- E Gao - Department of Pharmacology, MCP, Allegheny University of Health Sciences, Philadelphia, PA 19129, USAD L SnyderM D JohnsonE FriedmanJ RobertsJ Horwitz
- Publication Details
- Journal of molecular and cellular cardiology, Vol.29(2), pp.593-602
- Publisher
- England
- Grant note
- K07 AG 00532 04 / NIA NIH HHS N01MH30003 / NIMH NIH HHS AG 11060 / NIA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Identifiers
- 991014877831504721
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InCites Highlights
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- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Cell Biology