Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart

A. M. Feldman, A. E. Cates, W. B. Veazey, R. E. Hershberger, M. R. Bristow, K. L. Baughman, William A Baumgartner, C. Van Dop

Research output: Contribution to journalArticle

Abstract

Human heart failure is associated with a diminished contractile response to β-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (αG40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (G(s)). The increased activity in αG40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased αG40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to β1-adrenergic agonists in the failing human heart.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalJournal of Clinical Investigation
Volume82
Issue number1
StatePublished - 1988

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Pertussis Toxin
GTP-Binding Proteins
Adrenergic Agonists
Myocardium
Guanylyl Imidodiphosphate
Bacterial Toxins
Adenylyl Cyclases
Adenosine Diphosphate
Carrier Proteins
Heart Failure

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Feldman, A. M., Cates, A. E., Veazey, W. B., Hershberger, R. E., Bristow, M. R., Baughman, K. L., ... Van Dop, C. (1988). Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. Journal of Clinical Investigation, 82(1), 189-197.

Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. / Feldman, A. M.; Cates, A. E.; Veazey, W. B.; Hershberger, R. E.; Bristow, M. R.; Baughman, K. L.; Baumgartner, William A; Van Dop, C.

In: Journal of Clinical Investigation, Vol. 82, No. 1, 1988, p. 189-197.

Research output: Contribution to journalArticle

Feldman, AM, Cates, AE, Veazey, WB, Hershberger, RE, Bristow, MR, Baughman, KL, Baumgartner, WA & Van Dop, C 1988, 'Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart', Journal of Clinical Investigation, vol. 82, no. 1, pp. 189-197.
Feldman AM, Cates AE, Veazey WB, Hershberger RE, Bristow MR, Baughman KL et al. Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. Journal of Clinical Investigation. 1988;82(1):189-197.
Feldman, A. M. ; Cates, A. E. ; Veazey, W. B. ; Hershberger, R. E. ; Bristow, M. R. ; Baughman, K. L. ; Baumgartner, William A ; Van Dop, C. / Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 1. pp. 189-197.
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AU - Cates, A. E.

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AU - Hershberger, R. E.

AU - Bristow, M. R.

AU - Baughman, K. L.

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AU - Van Dop, C.

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AB - Human heart failure is associated with a diminished contractile response to β-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (αG40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (G(s)). The increased activity in αG40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased αG40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to β1-adrenergic agonists in the failing human heart.

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