Heterogeneous regulatory changes in cell surface membrane receptors coupled to a positive inotropic response in the failing human heart

  • M. R. Bristow
  • R. Ginsburg
  • E. M. Gilbert
  • R. E. Hershberger
Conference paper


The failing human ventricular myocardium undergoes heterogeneous changes at the receptor level that have some impact on the ability of the failing myocardium to respond to inotropic stimuli. In the failing human ventricular myocardium the β l-adrenergic receptor is profoundly down-regulated, the β 2-adrenergic receptor is only slightly decreased, α l-adrenergic receptors are unchanged and VIP receptors appear to be increased in density or affinity. These changes have implications for therapeutic strategies for heart failure and for the natural history and pathogenesis of heart muscle disease.


Adenylate Cyclase Vasoactive Intestinal Peptide Human Heart Creatine Kinase Activity Vasoactive Intestinal Peptide Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bristow MR, Cubicciotti R, Ginsburg R, Stinson EB, Johnson C (1982) Histamine-mediated adenylate cyclase stimulation in human myocardium. Mol Pharmacol 21: 671–679PubMedGoogle Scholar
  2. 2.
    Bristow MR, Ginsburg R, Minobe WA, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB (1982) Decreased catecholamine sensitivity and ß-adrenergic receptor density in failing human hearts. New Engl J Med 307: 205–211PubMedCrossRefGoogle Scholar
  3. 3.
    Bristow MR (1984) The adrenergic nervous system in heart failure. N Engl J Med 311 (13): 850–851PubMedCrossRefGoogle Scholar
  4. 4.
    Bristow MR, Ginsburg R, Strosberg A, Montgomery W, Minobe W (1984) Cardiovascular pharmacology and inotropic potential of forskolin in the human heart. J Clin Invest 74: 212–223PubMedCrossRefGoogle Scholar
  5. 5.
    Bristow MR, Laser JA, Ginsburg R, Minobe W (1985) ßs and ß2 receptors are coupled to adenylate cyclase in human ventricular myocardium. Clin Res 33(2):171AGoogle Scholar
  6. 6.
    Bristow MR, Minobe W, Rasmussen R (1985) Differential regulation of alpha and beta-adrenergic receptors in the failing human heart. Circulation [Suppl III] 72: 1315Google Scholar
  7. 7.
    Bristow MR, Ginsburg R (1985) ß2 receptors are present on myocardial cells in human ventricular myocardium. Am J Cardiol 57: 3F - 6FCrossRefGoogle Scholar
  8. 8.
    Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shah P, Jamieson S, Stinson EB (1986) Down-regulation in heart failure. Circ Res 59: 297–309PubMedCrossRefGoogle Scholar
  9. 9.
    Fowler MB, Laser JA, Hopkins G, Minobe W, Bristow MR (1986) Assessment of the ß-adrenergic receptor pathway in the intact failing human heart: Progressive receptor down-regulation and subsensitivity to agonist response. Circulation 74 (6): 1290–1302PubMedCrossRefGoogle Scholar
  10. 10.
    Ginsburg R, Bristow MR, Billingham ME, Stinson EB, Schroeder JS, Harrison DC (1983) Study of the normal and failing isolated human heart: Decreased response of failing heart to isoproterenol. Am Heart J 106: 535–540Google Scholar
  11. 11.
    Hershberger RE, Bristow MR (1986) Failing human left ventricular myocardium is supersensitive to vasoactive intestinal peptide. Clin Res 34 (2): 630AGoogle Scholar
  12. 12.
    Levey GS, Epstein SE (1969) Activation of adenyl cyclase by glucagon in cat and human heart. Circ Res 24: 151–156PubMedCrossRefGoogle Scholar
  13. 13.
    Munson PJ, Rodbard D (1980) LIGAND: A versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 107: 220–239PubMedCrossRefGoogle Scholar
  14. 14.
    Salomon Y, Londos C, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58: 541–548PubMedCrossRefGoogle Scholar
  15. 15.
    Taton G, Chatelain P, Delhaye M, Camus JC, De Neef P, Waelbroeck M, Tatemoto K, Robberecht P, Christophe J (1982) Vasoactive intestinal peptide (VIP) and peptide having N-terminal histidine and C-terminal isoleucine amide ( PHI) stimulate adenylate cyclase activity in human heart membranes. Peptides 3: 897–900PubMedCrossRefGoogle Scholar
  16. 16.
    Tsujimoto G, Bristow MR, Hoffman BB (1984) Identification of alphas-adrenergic receptors in rabbit aorta with 125[I]BE2254. Life Sci 34: 639–646PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • M. R. Bristow
    • 1
    • 2
  • R. Ginsburg
    • 1
  • E. M. Gilbert
    • 1
  • R. E. Hershberger
    • 1
  1. 1.Cardiology DivisionUniversity of Utah, School of MedicineSalt Lake CityUSA
  2. 2.Cardiology Division, 4A-100University of Utah Medical CenterSalt Lake CityUSA

Personalised recommendations