Betamethasone increases the β-adrenergic receptor density of human polymorphonuclear leukocytes

  • Gianni Marone
  • Biagio Fimiani
  • Rosaria Petracca
  • Edoardo Marchese
  • Mario Condorelli
Original Contributions


Prolonged incubation (18h) of human polymorphonuclear leukocytes (PMNs) with betamethasone (BT)(10−7 M) increased (3H)-DHA binding to human PMN membranes, apparently causing an increase in the number of β-adrenergic receptors. Inhibition of this effect by cycloheximide (2 µg/ml) suggests that it is dependent on protein synthesis. BT had no effect on basal levels of cAMP in PMNs, but synergistically potentiated the increase in cyclic AMP (cAMP) induced by isoproterenol. Propranolol completely abolished the synergistic effect of BT plus isoproterenol, suggesting that the potentiating effect of BT on cAMP metabolism required the activation of β-adrenergic receptors. Thus, BT increased the number of β-adrenergic receptors in human PMN membranes and potentiated the cAMP changes induced by β-agonists.


β-adrenergic receptor Betamethasone Corticosteroids Cyclic AMP Polymorphonuclear leukocytes 


  1. 1.
    Balow J. E., Hunninghake G. W., Fauci A. S.: Corticosteroids in human lymphocyte-mediated cytotoxic reactions — Transplantation23, 322, 1977.PubMedCrossRefGoogle Scholar
  2. 2.
    Brown B. L., Albano J. D. M., Ekins R. P., Sgherzi A. M., Tampion W.: A simple and sensitive saturation assay method for the measurement of adenosine 3′,5′-cyclic monophosphate — Biochem. J.121, 561, 1971.PubMedGoogle Scholar
  3. 3.
    Cheng J. B., Goldfien A., Ballard P. L., Roberts J. M.: Glucocorticoids increase pulmonary β-adrenergic receptors in fetal rabbit — Endocrinology107, 1646, 1980.PubMedGoogle Scholar
  4. 4.
    Davies A. O., Lefkowitz R. J.: Corticosteroid-induced differential regulation of β-adrenergic receptors in circulating human polymorphonuclear leukocytes and mononuclear leukocytes — J. clin. Endocrinol.51, 599, 1980.Google Scholar
  5. 5.
    Davies A. O., Lefkowitz R. J.: Agonist-promoted high affinity state of the β-adrenergic receptor in human neutrophils: modulation by corticosteroids — J. clin. Endocrinol.53, 703, 1981.CrossRefGoogle Scholar
  6. 6.
    Davies A. O., Lefkowitz R. J.:In vitro desensitization of β-adrenergic receptors in human neutrophils — J. clin. Invest.71, 565, 1983.PubMedCrossRefGoogle Scholar
  7. 7.
    Fantus I. G., Saviolakis G. A., Hedo J. A., Gorden P.: Mechanism of glucocorticoid-induced increase in insulin receptors of cultured human lymphocytes — J. biol. Chem.257, 8277, 1982.PubMedGoogle Scholar
  8. 8.
    Fauci A. S., Dale D. C.: The effect ofin vivo hydrocortisone on subpopulations of human lymphocytes — J. clin. Invest.53, 240, 1974.PubMedCrossRefGoogle Scholar
  9. 9.
    Fraser C. M., Venter J. C.: The synthesis of β-adrenergic receptors in cultured human lung cells: induction by glucocorticoids — Biochem. biophys. Res. Commun.94, 390, 1980.PubMedCrossRefGoogle Scholar
  10. 10.
    Galant S. P., Duriseti L., Underwood S., Allred S., Insel P. A.: Beta adrenergic receptors of polymorphonuclear particulates in bronchial asthma — J. clin. Invest.65, 577, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Hammerschmidt D. E., White J. G., Craddock P. R., Jacob H. S.: Corticosteroids inhibit complement-induced granulocyte aggregation — J. clin. Invest.63, 798, 1979.PubMedCrossRefGoogle Scholar
  12. 12.
    Lichtenstein L. M., Margolis S.: Histamine releasein vitro: inhibition by catecholamines and methylxanthines — Science161, 902, 1968.PubMedCrossRefGoogle Scholar
  13. 13.
    Lowry O. H., Rosenbrough N. J., Farr A. L., Randall R. J.: Protein measurement with Folin-phenol reagent — J. biol. Chem.193, 265, 1951.PubMedGoogle Scholar
  14. 14.
    Mano K., Akbarzadeh A., Townley R. G.: Effect of hydrocortisone on β-adrenergic receptors in lung membranes — Life Sci.25, 1925, 1979.PubMedCrossRefGoogle Scholar
  15. 15.
    Marone G., Plaut M., Lichtenstein L. M.: Characterization of a specific adenosine receptor on human lymphocytes — J. Immunol.121, 2153, 1978.PubMedGoogle Scholar
  16. 16.
    Marone G., Thomas L. L., Lichtenstein L. M.: The role of agonists that activate adenylate cyclase in the control of cAMP metabolism and enzyme release by human polymorphonuclear leukocytes — J. Immunol.125, 2277, 1980.PubMedGoogle Scholar
  17. 17.
    Marone G., Lichtenstein L. M., Plaut M.: Hydrocortisone and human lymphocytes: increases in cyclic AMP and potentiation of adenylate cyclase-activating agents — J. Pharmacol. exp. Ther.215, 469, 1980.PubMedGoogle Scholar
  18. 18.
    Marone G., Findlay S. R., Lichtenstein L. M.: Modulation of histamine release from human basophilsin vitro by physiological concentrations of zinc — J. Pharmacol. exp. Ther.217, 292, 1981.PubMedGoogle Scholar
  19. 19.
    Marone G., Poto S., Petracca R., Triggiani M., De Lutio di Castelguidone E., Condorelli M.: Activation of human basophils by staphylococcal protein A. I. The role of cyclic AMP, arachidonic acid metabolites, microtubules and microfilaments — Clin. exp. Immunol.50, 661, 1982.PubMedGoogle Scholar
  20. 20.
    Marone G., Columbo M., Poto S., Condorelli M.: Inhibition of histamine release from human basophilsin vitro by calmodulin antagonists — Clin. Immunol. Immunopathol.28, 334, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Marone G., Columbo M., Soppelsa L., Condorelli M.: The mechanism of basophil histamine release induced by pepstatin A — J. Immunol.133, 1542, 1984.PubMedGoogle Scholar
  22. 22.
    Marone G., Vigorita S., Antonelli C., Torella G., Genovese A., Condorelli M.: Evidence for an adenosine A2/Ra receptor on human basophils — Life Sci.36, 339, 1985.PubMedCrossRefGoogle Scholar
  23. 23.
    Meurs H., Van Den Bogaard W., Kauffman H. F., Bruynzeel P. L. B.: Characterization of (−)-(3H)-dihydroalprenolol binding to intact and broken cell preparations of human peripheral blood lymphocytes — Europ. J. Pharmacol.85, 185, 1982.CrossRefGoogle Scholar
  24. 24.
    Parrillo J. E., Fauci A. S.: Mechanisms of glucocorticoid action on immune processes — Ann. Rev. Pharmacol. Toxicol.19, 179 1979.CrossRefGoogle Scholar
  25. 25.
    Scatchard G.: The attractions of proteins for small molecules and ions — Ann. N. Y. Acad. Sci.51, 660, 1949.CrossRefGoogle Scholar
  26. 26.
    Smith J. W., Steiner A. L., Parker C. W.: Human lymphocyte metabolism. Effects of cyclic and non-cyclic nucleotides on stimulation by phytohemagglutinin — J. clin. Invest.50, 442, 1971.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Gianni Marone
    • 1
  • Biagio Fimiani
    • 1
  • Rosaria Petracca
    • 1
  • Edoardo Marchese
    • 1
  • Mario Condorelli
    • 1
  1. 1.I Clinica Medica, II Facoltà di Medicina e ChirurgiaUniversità degli Studi di NapoliNapoliItalia

Personalised recommendations