| Title |
Structure-bias relationships for fenoterol stereoisomers in six molecular and cellular assays at the β2-adrenoceptor
|
|---|---|
| Published in |
Naunyn-Schmiedeberg's Archives of Pharmacology, October 2014
|
| DOI | 10.1007/s00210-014-1054-5 |
| Pubmed ID | |
| Authors |
Michael T. Reinartz, Solveig Kälble, Timo Littmann, Takeaki Ozawa, Stefan Dove, Volkhard Kaever, Irving W. Wainer, Roland Seifert |
| Abstract |
Functional selectivity is well established as an underlying concept of ligand-specific signaling via G protein-coupled receptors (GPCRs). Functionally, selective drugs could show greater therapeutic efficacy and fewer adverse effects. Dual coupling of the β2-adrenoceptor (β2AR) triggers a signal transduction via Gsα and Giα proteins. Here, we examined 12 fenoterol stereoisomers in six molecular and cellular assays. Using β2AR-Gsα and β2AR-Giα fusion proteins, (R,S')- and (S,S')-isomers of 4'-methoxy-1-naphthyl-fenoterol were identified as biased ligands with preference for Gs. G protein-independent signaling via β-arrestin-2 was disfavored by these ligands. Isolated human neutrophils constituted an ex vivo model of β2AR signaling and demonstrated functional selectivity through the dissociation of cAMP accumulation and the inhibition of formyl peptide-stimulated production of reactive oxygen species. Ligand bias was calculated using an operational model of agonism and revealed that the fenoterol scaffold constitutes a promising lead structure for the development of Gs-biased β2AR agonists. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 30% |
| Student > Master | 4 | 20% |
| Student > Doctoral Student | 2 | 10% |
| Student > Ph. D. Student | 2 | 10% |
| Professor | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 3 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 20% |
| Biochemistry, Genetics and Molecular Biology | 4 | 20% |
| Agricultural and Biological Sciences | 4 | 20% |
| Chemistry | 3 | 15% |
| Engineering | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 4 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 September 2015.
All research outputs
#14,788,263
of 22,768,097 outputs
Outputs from Naunyn-Schmiedeberg's Archives of Pharmacology
#1,326
of 1,723 outputs
Outputs of similar age
#144,310
of 260,976 outputs
Outputs of similar age from Naunyn-Schmiedeberg's Archives of Pharmacology
#5
of 12 outputs
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So far Altmetric has tracked 1,723 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.