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Translocation and uncoupling of the beta-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo.

Publication ,  Journal Article
Strasser, RH; Stiles, GL; Lefkowitz, RJ
Published in: Endocrinology
October 1984

Beta-adrenergic agonists and antagonists are widely used in many clinical situations to regulate beta-adrenergic stimulation. However, responsiveness to beta-stimulation may be reduced by the process of desensitization. We have established an in vivo mammalian model system, the rat lung, to study the cellular and biochemical basis for beta-agonist induced desensitization. After in vivo administration of a beta-agonist [(-)isoproterenol] the adenylate cyclase becomes rapidly insensitive to further stimulation by beta-agonists with no change in basal or NaF-stimulated activity. The in vivo desensitization can be blocked by the simultaneous administration of a beta-antagonist [(+/-)propranolol] and the process displays the pharmacological characteristics typifying the beta 2 receptor of rat lung. This indicates that the in vivo desensitization is itself a receptor-mediated event. The processes of de- and resensitization are very rapid with onset within 5 min, maximal effect at 10 min, and complete reversal by 2-3 h. The change of adenylate cyclase sensitivity is paralleled by a translocation of approximately 40% of the beta-receptors from the plasma membrane fraction to a light membrane fraction, which has very low activities of plasma membrane marker enzymes. The receptors translocated to the light membrane fraction as well as those remaining in the plasma membranes are uncoupled with loss of their ability to form the high affinity, nucleotide sensitive, physiologically active state of the receptor. During resensitization the receptors in the plasma membrane fraction are recoupled before all the translocated receptors have returned. This suggests that translocation and uncoupling of the receptors are two distinct, probably independent processes. During the entire process of de- and resensitization no structural change of the receptor protein residing in the plasma membranes or light membrane fraction can be demonstrated as visualized by photoaffinity labeling.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

October 1984

Volume

115

Issue

4

Start / End Page

1392 / 1400

Location

United States

Related Subject Headings

  • Sodium Fluoride
  • Receptors, Adrenergic, beta
  • Rats, Inbred WKY
  • Rats
  • Propranolol
  • Pindolol
  • Nucleotidases
  • Norepinephrine
  • Molecular Weight
  • Male
 

Citation

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Strasser, R. H., Stiles, G. L., & Lefkowitz, R. J. (1984). Translocation and uncoupling of the beta-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo. Endocrinology, 115(4), 1392–1400. https://doi.org/10.1210/endo-115-4-1392
Strasser, R. H., G. L. Stiles, and R. J. Lefkowitz. “Translocation and uncoupling of the beta-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo.Endocrinology 115, no. 4 (October 1984): 1392–1400. https://doi.org/10.1210/endo-115-4-1392.
Strasser, R. H., et al. “Translocation and uncoupling of the beta-adrenergic receptor in rat lung after catecholamine promoted desensitization in vivo.Endocrinology, vol. 115, no. 4, Oct. 1984, pp. 1392–400. Pubmed, doi:10.1210/endo-115-4-1392.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

October 1984

Volume

115

Issue

4

Start / End Page

1392 / 1400

Location

United States

Related Subject Headings

  • Sodium Fluoride
  • Receptors, Adrenergic, beta
  • Rats, Inbred WKY
  • Rats
  • Propranolol
  • Pindolol
  • Nucleotidases
  • Norepinephrine
  • Molecular Weight
  • Male