Age Increases Expression and Receptor-Mediated Activation of Gα i in Human Atria

Jason D. Kilts, Toshimasa Akazawa, Habib E. El-Moalem, Joseph P. Mathew, Mark F. Newman, Madan M. Kwatra

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Recently, we demonstrated that β2AR and several other Gαs-coupled receptors in human atria also couple to Gαi, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Gαi in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Gαi. Right atrial appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82 ± 18% more Gαi2 than atria from mature adults (P < 0.002); this increase in Gαi with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [32P]azidoanilido-GTP. We also find that receptor-mediated activation of Gαi, is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Gαi with pertussis toxin, indicating that the age-dependent increases in Gα i expression and activation have functional consequences. Because β2ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Gαi may have a role in depressing cardiac function in aged human atria.

Original languageEnglish
Pages (from-to)662-670
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume42
Issue number5
DOIs
StatePublished - Nov 2003

Funding

FundersFunder number
National Institute on AgingR01AG015817

    Keywords

    • Adenylyl cyclase
    • Cardiac
    • Glucagons
    • Muscarinic
    • β-adrenergic

    ASJC Scopus subject areas

    • Pharmacology
    • Cardiology and Cardiovascular Medicine

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