Homologous desensitization of beta-adrenergic receptor coupled adenylate cyclase. Resensitization by polyethylene glycol treatment.

Journal Article (Journal Article)

Brief (approximately 20-min) exposure of S49 lymphoma cells to beta-agonists such as isoproterenol leads to a homologous form of desensitization in which beta-agonist but not prostaglandin E1-sensitive or NaF-sensitive adenylate cyclase is reduced. The desensitized receptors (R) appear to be sequestered away from the effector system (guanine nucleotide regulatory protein (Ns) and adenylate cyclase (C)). Membrane perturbants such as polyethylene glycol are known to reorient membrane proteins and lipids. Thus, we fused agonist-desensitized S49 lymphoma cells to each other, using polyethylene glycol as fusogen, in an attempt to functionally reunite the R, N, and C components which might have become sequestered in microdomains of the plasma membrane during desensitization. Such treatment completely restored isoproterenol-stimulated adenylate cyclase to normal and re-established the ability of R and N to functionally couple as assessed by the ability to form a high affinity, guanine nucleotide-sensitive state of the receptor. These results support the concept that agonist-promoted sequestration plays a functionally significant role in the homologous desensitization of the beta-adrenergic receptor.

Full Text

Duke Authors

Cited Authors

  • Strasser, RH; Lefkowitz, RJ

Published Date

  • April 25, 1985

Published In

Volume / Issue

  • 260 / 8

Start / End Page

  • 4561 - 4564

PubMed ID

  • 2985555

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States