Beta-adrenergic receptor sequestration. A potential mechanism of receptor resensitization.

Published

Journal Article

Continuous exposure of cells to hormonal agonists often causes a rapid waning of the stimulated response. This desensitization effect has been extensively studied in the beta-adrenergic receptor system, and attributed largely to the rapid phosphorylation of the receptor by two kinases. Over a similar time frame (seconds to minutes), agonists also trigger a selective loss in the capacity of receptors to bind hydrophilic but not hydrophobic ligands, a phenomenon termed sequestration. There is some evidence suggesting that sequestration represents the rapid internalization of receptors, but the functional significance of sequestration has remained unclear. Upon the removal of agonist, both desensitization and sequestration are readily reversed with similar kinetics (t1/2 approximately 3 min for both). To investigate the possibility that receptor sequestration is involved in this resensitization of the adenylyl cyclase response, we applied two distinct approaches to block receptor sequestration: by pretreating cells with sucrose and by creating a sequestration-defective beta 2-adrenergic receptor by site-specific mutagenesis. Both approaches effectively disabled receptor sequestration, with little effect on adenylyl cyclase stimulation or on desensitization. However, in both cases, no recovery from desensitization was apparent even 20 min after the removal of agonist. Similarly, pretreating cells with concanavalin A almost completely blocked receptor sequestration and resensitization but only partially inhibited other receptor functions. Our results therefore suggest that sequestration of beta 2-adrenergic receptors is a mechanism involved in reactivating and recycling desensitized receptors.

Full Text

Duke Authors

Cited Authors

  • Yu, SS; Lefkowitz, RJ; Hausdorff, WP

Published Date

  • January 5, 1993

Published In

Volume / Issue

  • 268 / 1

Start / End Page

  • 337 - 341

PubMed ID

  • 8380158

Pubmed Central ID

  • 8380158

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States