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In vitro desensitization of beta adrenergic receptors in human neutrophils. Attenuation by corticosteroids.

Publication ,  Journal Article
Davies, AO; Lefkowitz, RJ
Published in: J Clin Invest
March 1983

The receptor alterations involved in catecholamine-induced desensitization of adenylate cyclase in human neutrophils have been investigated as has the ability of hydrocortisone to modify such alterations. Incubation of human neutrophils with isoproterenol for 3 h in vitro resulted in an 86% reduction in the ability of isoproterenol to stimulate cyclic AMP accumulation in the cells. Two types of receptor alterations were documented. There was a 40% reduction in the number of beta adrenergic receptors (42 vs. 25 fmol/mg protein, P < 0.005) present after desensitization as assessed by [(3)H]dihydroalprenolol ([(3)H]DHA) binding. In addition the receptors appeared to be relatively uncoupled from adenylate cyclase. This uncoupling was assessed by examining the ability of the agonist isoproterenol to stabilize a high-affinity form of the receptor, detected by computer modelling of competition curves for [(3)H]DHA binding. Desensitized receptors were characterized by rightward-shifted agonist competition curves. When hydrocortisone was added to the desensitizing incubations (combined treatment) there was a statistically significant attenuation in the desensitization process as assessed by the ability of isoproterenol to increase cyclic AMP levels in the cells. Although combined treatment did not prevent the decline in receptor number, it did attenuate the uncoupling of the receptors. Combined treatment resulted in competition curves intermediate between the control and the rightward-shifted desensitization curves. Prednisolone was similar to hydrocortisone in attenuating isoproterenol-induced uncoupling. Thus, steroids appeared to attenuate agonist-induced desensitization of the beta adrenergic receptor-adenylate cyclase system by dampening the ability of agonists to uncouple receptors without modifying their ability to promote down-regulation of beta adrenergic receptors.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1983

Volume

71

Issue

3

Start / End Page

565 / 571

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Neutrophils
  • Male
  • Isoproterenol
  • Immunology
  • Hydrocortisone
  • Humans
  • Female
  • Cyclic AMP
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Davies, A. O., & Lefkowitz, R. J. (1983). In vitro desensitization of beta adrenergic receptors in human neutrophils. Attenuation by corticosteroids. J Clin Invest, 71(3), 565–571. https://doi.org/10.1172/jci110801
Davies, A. O., and R. J. Lefkowitz. “In vitro desensitization of beta adrenergic receptors in human neutrophils. Attenuation by corticosteroids.J Clin Invest 71, no. 3 (March 1983): 565–71. https://doi.org/10.1172/jci110801.
Davies, A. O., and R. J. Lefkowitz. “In vitro desensitization of beta adrenergic receptors in human neutrophils. Attenuation by corticosteroids.J Clin Invest, vol. 71, no. 3, Mar. 1983, pp. 565–71. Pubmed, doi:10.1172/jci110801.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1983

Volume

71

Issue

3

Start / End Page

565 / 571

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Neutrophils
  • Male
  • Isoproterenol
  • Immunology
  • Hydrocortisone
  • Humans
  • Female
  • Cyclic AMP