Year: 2011
Type: article
Abstract: The β(2)-adrenergic receptor (β(2)AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β(2)AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β(2)AR desensitization at the whole cell level.
Source: PLoS ONE
Authors: Vasiliy Goral, Yan Jin, Haiyan Sun, Ann M. Ferrie, Qi Wu, Ye Fang
Institution: Corning (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
OpenAlex ID: W2017785769