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β-Adrenoceptor and adenylate cyclase regulation in cardiac myocyte growth

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Summary

We studied the effect of growth on β-adrenergic receptor properties of neonatal rat heart myocytes cultured in serum-free medium with transferrin and insulin. Growth was induced by addition of 1 μM (−)-norepinephrine for two days, 200 nM of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for two days, or 30 nM T3 for six days. The Kd values for β-receptor binding (125I-ICYP) were unaffected by growth. The maximum number of β-receptor binding sites calculated as sites/cell was increased 1.47-fold by T3 (p<.005), but was decreased to 54% of control values by (−)-norepinephrine (p<.005); TPA had no effect on either Kd or Bmax values. (−)-Isoproterenol-stimulated adenylate cyclase activity was augmented only in membranes from T3-treated cells and was reduced by 69% in membranes from (−)-norepinephrine treated cells. TPA had no effect on

(−)-isoproterenol-stimulated adenylate cyclase activity. We conclude that the mechanisms controlling β-adrenergic receptor number may be distinct from those controlling growth, since receptor number does not correlate with cell enlargement. Furthermore, in (−)-norepinephrine-stimulated growth, which we have shown previously is an α1-adrenoceptor mediated response, β-adrenergic signal transduction is modulated in a directionally opposite fashion.

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Author notes

  1. J. S. Karliner M.D. (Professor of Medicine, Chief)

    Present address: Cardiology Service of the Veterans Administration Medical Center, 4150 Clement Street, 94121, San Francisco, CA

Authors and Affiliations

  1. Cardiology Service of the Veterans Administration Medical Center, 4150 Clement Street, 94121, San Francisco, CA

    P. C. Simpson

  2. Cardiovascular Research Institute, University of California, San Francisco, USA

    J. S. Karliner M.D. (Professor of Medicine, Chief) & P. C. Simpson

  3. Department of Medicine, University of California, San Francisco, USA

    J. S. Karliner M.D. (Professor of Medicine, Chief) & P. C. Simpson

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Supported by grants from the Veterans Administration Research Service, American Heart Association California Affiliate, and National Heart, Lung, and Blood Institute Grant HL31113. Dr. Simpson is a Clinical Investigator of the Veterans Administration Research Service.

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Karliner, J.S., Simpson, P.C. β-Adrenoceptor and adenylate cyclase regulation in cardiac myocyte growth. Basic Res Cardiol 83, 655–663 (1988). https://doi.org/10.1007/BF01906960

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