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Functional integrity of desensitized beta-adrenergic receptors.

Publication ,  Journal Article
Strulovici, B; Stadel, JM; Lefkowitz, RJ
Published in: J Biol Chem
May 25, 1983

The adenylate cyclase-coupled beta 2-adrenergic receptor of the frog erythrocyte has served as a useful model system for elucidating the mechanisms of catecholamine-induced densensitization. In this system, it has been previously demonstrated that agonist-induced refractoriness is associated with sequestration of the beta-adrenergic receptors in vesicles away from the cell surface and from their effector unit, the adenylate cyclase system (Stadel, J.M., Strulovici, B., Nambi, P., Lavin, T.N., Briggs, M.M., Caron, M.G., and Lefkowitz, R.J. (1983) J. Biol. Chem. 258, 3032-3038). These internalized beta-adrenergic receptors appear to be structurally intact as assessed by photoaffinity labeling, but their functional status has previously been unknown. In the present studies, we sought to assess the functionality of the sequestered vesicular receptors by fusing them to Xenopus laevis erythrocytes. This cell is suitable for such studies, since it has almost no detectable beta-adrenergic receptor or catecholamine-sensitive adenylate cyclase, but contains prostaglandin E1-stimulable adenylate cyclase. Fusion of beta-adrenergic receptor-containing vesicles from desensitized frog erythrocytes with X. laevis erythrocytes results in a 30-fold stimulation of the hybrid adenylate cyclase by the beta-adrenergic agonist isoproterenol. This effect was entirely blocked by the beta-antagonist propranolol. The catecholamine-sensitive adenylate cyclase activity established in the vesicle-Xenopus hybrids showed the characteristic agonist potency series of the donor frog erythrocyte beta 2-adrenergic receptor. Fusion of vesicles from desensitized frog erythrocytes in which the beta-adrenergic receptors had been inactivated with the group specific reagent dicyclohexylcarbodiimide, or of vesicles derived from control frog erythrocytes, which contain low amounts of beta-adrenergic receptor, did not establish catecholamine-sensitive adenylate cyclase activity in the hybrids. These data demonstrate that beta-adrenergic receptors internalized during desensitization retain their functionality when recoupled to an adenylate cyclase system from a different source. The functional uncoupling of these receptors during desensitization is thus more likely due to their sequestration away from the other components of the adenylate cyclase than to any alterations in the receptors themselves.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 25, 1983

Volume

258

Issue

10

Start / End Page

6410 / 6414

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Rana pipiens
  • Prostaglandins E
  • Propranolol
  • Isoproterenol
  • Fluorides
  • Erythrocytes
  • Cell Fusion
 

Citation

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MLA
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Strulovici, B., Stadel, J. M., & Lefkowitz, R. J. (1983). Functional integrity of desensitized beta-adrenergic receptors. J Biol Chem, 258(10), 6410–6414.
Strulovici, B., J. M. Stadel, and R. J. Lefkowitz. “Functional integrity of desensitized beta-adrenergic receptors.J Biol Chem 258, no. 10 (May 25, 1983): 6410–14.
Strulovici B, Stadel JM, Lefkowitz RJ. Functional integrity of desensitized beta-adrenergic receptors. J Biol Chem. 1983 May 25;258(10):6410–4.
Strulovici, B., et al. “Functional integrity of desensitized beta-adrenergic receptors.J Biol Chem, vol. 258, no. 10, May 1983, pp. 6410–14.
Strulovici B, Stadel JM, Lefkowitz RJ. Functional integrity of desensitized beta-adrenergic receptors. J Biol Chem. 1983 May 25;258(10):6410–6414.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

May 25, 1983

Volume

258

Issue

10

Start / End Page

6410 / 6414

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Rana pipiens
  • Prostaglandins E
  • Propranolol
  • Isoproterenol
  • Fluorides
  • Erythrocytes
  • Cell Fusion