Direct demonstration of impaired functionality of a purified desensitized beta-adrenergic receptor in a reconstituted system.

Published

Journal Article

Long-term exposure of various cell types to beta-adrenergic agonists such as isoproterenol leads to an attenuated responsiveness ("desensitization") of the adenylate cyclase system to further challenge with these agonists. The turkey erythrocyte model system was used earlier to show that a covalent modification of the receptor (phosphorylation) is associated with this process. The functionality of the "desensitized" beta-adrenergic receptor was assessed by implanting purified beta-adrenergic receptor preparations from control and desensitized turkey erythrocytes into phospholipid mixtures and then fusing them with receptor-deficient cells (Xenopus laevis erythrocytes). Desensitized beta-adrenergic receptors showed a 40 to 50 percent reduction in their ability to couple to the heterologous adenylate cyclase system, comparable to the reduction in their functionality observed in their original membrane environment. These results demonstrate the utility of recently developed receptor reconstitution techniques for assessing the functionality of purified receptors and show a direct link between a covalent modification of a membrane-bound receptor and its impaired functionality in a reconstituted system.

Full Text

Duke Authors

Cited Authors

  • Strulovici, B; Cerione, RA; Kilpatrick, BF; Caron, MG; Lefkowitz, RJ

Published Date

  • August 24, 1984

Published In

Volume / Issue

  • 225 / 4664

Start / End Page

  • 837 - 840

PubMed ID

  • 6089331

Pubmed Central ID

  • 6089331

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.6089331

Language

  • eng

Conference Location

  • United States