Biological maturation and β-adrenergic effectors: development of β-adrenergic receptors in rabbit heart

  • William Schumacher
  • Bernard L. Mirkin
  • J. R. Sheppard
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 4)

Summary

The β-adrenergic receptor, transduction processes and catalytic activity of the adenylate cyclase enzyme complex have been investigated in rabbit heart at different stages of biological maturation. The binding of [3H]-dihydroalprenolol to a washed membrane preparation isolated from rabbit ventricular muscle was used to characterize β-adrenergic receptors. Significant age-related differences were noted in β-receptor affinity (Kd) and density (RD) of neonatal and adult animals; the adult Kd was 3.7-fold greater and the RD 2-fold higher than the neonates. No significant differences in these parameters were detected among the 27-day old fetus and the 1- and 7-day old neonates. Age-dependent differences in agonist isoproterenol affinity for the receptor were not observed in contrast to the significant changes in antagonist (DHA) affinity.

Age-related changes in receptor affinity were also quantitated by determining the inhibitory potency of alprenolol on isoproterenol stimulated adenylate cyclase enzyme activity. A decreased affinity of the β-adrenergic receptor for alprenolol in the adult heart was indicated by a 3.7-fold greater Ki for the adult than the 1-day old neonate. Ontogenic variations in the coupling efficiency between the receptor and catalytic components of the adenylate cyclase complex were also evaluated. The Kd of the β-adrenergic receptor for isoproterenol and the EC50 for adenylate cyclase stimulation were determined under similar conditions. The corresponding coupling index (Kd/ EC50) was found to be 2.4-fold greater in the 1-day old neonate than adult, suggesting that for a given percentage increase in adenylate cyclase activity, a lower percentage of β-adrenergic receptor sites need be occupied in the neonate. These data extend previous studies (29) and indicate all components of the rabbit heart adenylate cyclase enzyme complex (i.e., the β-adrenergic receptor, the GTP-dependent transduction event, and the catalytic subunit) exhibit significant developmental changes.

Keywords

Manifold Leukemia Adenosine Norepinephrine Polystyrene 

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References

  1. 1.
    Alexander, W. R., Williams, L. T. and Lefkowitz, R. J., 1975. Proc. Natl. Acad. Sci. U.S.A. 72: 1564–1568.PubMedCrossRefGoogle Scholar
  2. 2.
    Aurback, G. P., Fedak, S. A., Woodward, C. J., Palmer, J. S., Hauser, D. and Troxler, F., 1974. Science 186: 1223–1224.CrossRefGoogle Scholar
  3. 3.
    Baker, S. D. and Potter, L. T., 1980. Br. J. Pharmacol. 68: 65–70.PubMedGoogle Scholar
  4. 4.
    Brown, B. L., Albano, J. D. M., Ekins, R. P. and Sgherzi, A. M., 1971. Biochem. J. 121: 561–562.PubMedGoogle Scholar
  5. 5.
    Chen, F. C. M., Yamamura, H. I. and Roeske, W. R., 1979. Eur. J. Pharmacol. 58: 255–264.PubMedCrossRefGoogle Scholar
  6. 6.
    Ciaraldi, T. and Marinetti, G. V., 1977. Biochem. Biophys. Res. Commun. 74: 984–991.PubMedCrossRefGoogle Scholar
  7. 7.
    Claycomb, W. C., 1976. J. Biol. Chem. 251: 6082–6089.PubMedGoogle Scholar
  8. 8.
    Coleman, A. J., Paterson, D. S. and Somerville, A. R., 1979. Biochem. Pharmacol. 128: 1011–1013.CrossRefGoogle Scholar
  9. 9.
    Coleman, A. J. and Somerville, A. R., 1977. Br. J. Pharmacol. 59: 83–93.PubMedGoogle Scholar
  10. 10.
    Friedman, W. F., Pool, P. E., Jacobowitz, D., Seagren, S. C. and Braunwald, E., 1968. Circ. Res. 23: 25–32.PubMedGoogle Scholar
  11. 11.
    Glaubiger, G., Tsai, B. S. and Lefkowitz, R. J., 1978. Nature 273: 240–242.PubMedCrossRefGoogle Scholar
  12. 12.
    Green, T. D., O’Dea, R. F. and Mirkin, B. L., 1979. Ann. Rev. Pharmacol. Toxicol. 19: 285–322.CrossRefGoogle Scholar
  13. 13.
    Howlett, A. C., VanArsdale, P. M. and Gilman, A. G., 1978. Mol. Pharmacol. 14: 531–539.PubMedGoogle Scholar
  14. 14.
    Kaumann, A. J. and Birnbaumer, L., 1973. Acta Phys. Lat. Amer. 23: 619–620.Google Scholar
  15. 15.
    Krall, J. F., Connelly, M. and Tuck, M. L., 1980. J. Pharmacol. Exp. Ther. 214: 554–560.PubMedGoogle Scholar
  16. 16.
    Krawietz, W., Poppert, D., Erdmann, E., Glossmann, H., Struck, C. J. and Konrad, C., 1976. Naunyn Schmiedeberg Arch. Pharmacol. 295: 215–224.CrossRefGoogle Scholar
  17. 17.
    Krawietz, W., Weinsteiger, M., Pruchniewski, M. and Erdmann, E., 1979. Biochem. Pharmacol. 28: 2999–3007.PubMedCrossRefGoogle Scholar
  18. 18.
    Limas, C. and Limas, C. J., 1978. Biochem. Biophys. Res. Commun. 83: 710–714.PubMedCrossRefGoogle Scholar
  19. 19.
    Lowry, O. H., Rosebrough, W. J. and Randall, R. J., 1951. J. Biol. Chem. 193: 265–289.PubMedGoogle Scholar
  20. 20.
    Lucas and Bockaert, J., 1977. Mol. Pharmacol. 13: 314–329. 314–329.PubMedGoogle Scholar
  21. 21.
    Maguire, M. E., Ross, E. M. and Gilman, A. G., 1977. Adv. Cyclic Nucleotide Res. 8: 1–74.PubMedGoogle Scholar
  22. 22.
    Mayer, S. E., 1972. J. Pharmacol. Exp. Ther. 181: 116–125.PubMedGoogle Scholar
  23. 23.
    Mukherjee, C., Caron, M. G. and Coverstone, M., 1975. J. Biol. Chem. 250: 4869–4876.PubMedGoogle Scholar
  24. 24.
    Pappano, A. J., 1977. Pharmacol. Rev. 29: 3–33.PubMedGoogle Scholar
  25. 25.
    Roffi, J. and Motelica-Heino, I., 1975. Experientia (Basel) 31: 194–195.CrossRefGoogle Scholar
  26. 26.
    Ross, E. M. and Gilman, A. G., 1977. Proc. Natl. Acad. Sci. U.S.A. 74: 3715–3719.PubMedCrossRefGoogle Scholar
  27. 27.
    Scatchard, G., 1949. Ann. N.Y. Acad. Sci. 51: 660–672.CrossRefGoogle Scholar
  28. 28.
    Schild, H. O., 1947. J. Pharmacol. 2: 189–206.Google Scholar
  29. 29.
    Schumacher, W., Sheppard, J. R. and Mirkin, B. L., 1982. J. Pharmacol. Exp. Ther. 223: 587–593.PubMedGoogle Scholar
  30. 30.
    Slotkin, T. A., Smith, P. G., Lau, C. and Bareis, D. L., 1980. In: Biogenic Amines in Development (Parves, S. and Parves, H. eds.), Elsevier, North Holland, Amsterdam.Google Scholar
  31. 31.
    Snyder, F. F. and Drummond, G. I., 1978. Arch. Biochem. Biophys. 185: 116–125.PubMedCrossRefGoogle Scholar
  32. 32.
    W hitsett, J. A. and Darovec-Beckerman, L., 1981. Ped. Res. 15: 1363–1369.Google Scholar
  33. 33.
    Williams, L. T. and Lefkowitz, R. J., 1977. J. Biol. Chem. 252: 2787–2789.PubMedGoogle Scholar
  34. 34.
    Winek, R. and Bhalla, R., 1979. Biochem. Biophys. Res. Commun 91: 200–206.PubMedCrossRefGoogle Scholar
  35. 35.
    Yamada, S., Yamamura, H. I. and Roeske, W. R., 1980. Mol. Pharmacol. 18: 185–192.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • William Schumacher
    • 1
  • Bernard L. Mirkin
    • 1
  • J. R. Sheppard
    • 1
    • 2
  1. 1.Division of Clinical Pharmacology, Departments of Pharmacology and Pediatrics, Medical School, Department of Genetics and Cell Biology, Dight Institute for Human GeneticsUniversity of MinnesotaMinneapolisUSA
  2. 2.Dight Institute for Human GeneticsMinneapolisUSA

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