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. 1976 May;73(5):1494–1498. doi: 10.1073/pnas.73.5.1494

Desensitization of beta-adrenergic receptors by beta-adrenergic agonists in a cell-free system: resensitization by guanosine 5'-(beta, gamma-imino)triphosphate and other purine nucleotides.

C Mukherjee, R J Lefkowitz
PMCID: PMC430323  PMID: 5723

Abstract

Incubation of purified frog erythrocyte membranes with beta-adrenergic agonists at 25 degrees produces relatively rapid (half-time about 10 min) desensitization (inactivation) of about 60% of the beta-adrenergic receptor binding sites. The desensitized receptors no longer bind the specific beta-adrenergic ligand (-)[3H]dihydroalprenolol. The decrease in the number of functional beta-adrenergic receptors is also manifest as a decreased ability of isoproterenol to stimulate the membrane-bound adenylate cyclase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Franklin T. J., Foster S. J. Hormone-induced desensitisation of hormonal control of cyclic AMP levels in human diploid fibroblasts. Nat New Biol. 1973 Dec 5;246(153):146–148. doi: 10.1038/newbio246146a0. [DOI] [PubMed] [Google Scholar]
  2. Kebabian J. W., Zatz M., Romero J. A., Axelrod J. Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3735–3739. doi: 10.1073/pnas.72.9.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  4. Lefkowitz R. J. Stimulation of catecholamine-sensitive adenylate cyclase by 5'-guanylyl-imidodiphosphate. J Biol Chem. 1974 Oct 10;249(19):6119–6124. [PubMed] [Google Scholar]
  5. Londos C., Salomon Y., Lin M. C., Harwood J. P., Schramm M., Wolff J., Rodbell M. 5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3087–3090. doi: 10.1073/pnas.71.8.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mickey J., Tate R., Lefkowitz R. J. Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. J Biol Chem. 1975 Jul 25;250(14):5727–5729. [PubMed] [Google Scholar]
  7. Mukherjee C., Caron M. G., Coverstone M., Lefkowitz R. J. Identification of adenylate cyclase-coupled beta-adrenergic receptors in frog erythrocytes with (minus)-[3-H] alprenolol. J Biol Chem. 1975 Jul 10;250(13):4869–4876. [PubMed] [Google Scholar]
  8. Mukherjee C., Caron M. G., Lefkowitz R. J. Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites. Proc Natl Acad Sci U S A. 1975 May;72(5):1945–1949. doi: 10.1073/pnas.72.5.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mukherjee C., Caron M. G., Mullikin D., Lefkowitz R. J. Structure-activity relationships of adenylate cyclase-coupled beta adrenergic receptors: determination by direct binding studies. Mol Pharmacol. 1976 Jan;12(1):16–31. [PubMed] [Google Scholar]
  10. Newcombe D. S., Ciosek C. P., Jr, Ishikawa Y., Fahey J. V. Human synoviocytes: activation and desensitization by prostaglandins and 1-epinephrine. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3124–3128. doi: 10.1073/pnas.72.8.3124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rodbell M. On the mechanism of activation of fat cell adenylate cyclase by guanine nucleotides. An explanation for the biphasic inhibitory and stimulatory effects of the nucleotides and the role of hormones. J Biol Chem. 1975 Aug 10;250(15):5826–5834. [PubMed] [Google Scholar]
  12. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  13. Schreier M. H., Noll H. Conformational changes in ribosomes during protein synthesis. Proc Natl Acad Sci U S A. 1971 Apr;68(4):805–809. doi: 10.1073/pnas.68.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Spiegel A. M., Aurbach G. D. Binding of 5'-guanylyl-imidodiphosphate to turkey erythrocyte membranes and effects on beta-adrenergic-activated adenylate cyclase. J Biol Chem. 1974 Dec 10;249(23):7630–7636. [PubMed] [Google Scholar]
  15. Williams L. T., Snyderman R., Lefkowitz R. J. Identification of beta-adrenergic receptors in human lymphocytes by (-) (3H) alprenolol binding. J Clin Invest. 1976 Jan;57(1):149–155. doi: 10.1172/JCI108254. [DOI] [PMC free article] [PubMed] [Google Scholar]

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