Evidence map›Paper›PMID 24032557›Full record

ReviewBritish journal of pharmacology2013

Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor.

B Sivertsen, N Holliday, A N Madsen, B Holst

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Article
  3. G protein-coupled receptors and obesity.Frontiers in endocrinology · 2023
    Review
  4. Review
  5. Article
  6. Review
  7. Differential effects of functionally different histamine HNaunyn-Schmiedeberg's archives of pharmacology · 2018
    Article
  8. Translating biased signaling in the ghrelin receptor system into differential in vivo functions.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Ghrelin and motilin receptors as drug targets for gastrointestinal disorders.Nature reviews. Gastroenterology & hepatology · 2016
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

B SivertsenLaboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, the Panum Institute, University of Copenhagen, Copenhagen, Denmark.
N Holliday
A N Madsen
B Holst
University of Copenhagen · DKUniversity of Nottingham · GB

Funding

Medical Research Council G0700049
6 · The paper itself

Abstract

unlabelledThe ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several different signalling pathways including Gαq , Gαi/o , Gα12/13 and arrestin recruitment. These multiple signalling pathways allow for functionally biased signalling, where one signalling pathway may be favoured over another either by selective ligands or through mutations in the receptor. In the present review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have been demonstrated to signal more strongly through the Gαq -coupled pathway than the Gα12/13 -coupled pathway. Similarly a ligand that promotes Gαq coupling over Gαi coupling has been described and it has been suggested that several different active conformations of the receptor may exist dependent on the properties of the agonist. Importantly, ligands with such biased signalling properties may allow the development of drugs that selectively modulate only the therapeutically relevant physiological functions, thereby decreasing the risk of side effects. LINKED ARTICLES: This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

Indexed as

Drug DesignAnimalsAnti-Obesity AgentsAppetite RegulationEatingEnergy MetabolismHumansLigandsMolecular StructureObesityProtein ConformationReceptors, GhrelinSignal TransductionStructure-Activity RelationshipAnti-Obesity AgentsLigandsReceptors, Ghrelin7TM receptorbiased agonismbiased signallingghrelin receptorGPCR

Identifiers

PMID24032557
PMCPMC3838681
OpenAlexW1580261433

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.