Evidence map›Paper›PMID 25804845›Full record

ArticleMolecular pharmacology2015

Investigation of the fate of type I angiotensin receptor after biased activation.

Gyöngyi Szakadáti, András D Tóth, Ilona Oláh, László Sándor Erdélyi, Tamas Balla, Péter Várnai, László Hunyady, András Balla

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In one paragraph

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
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  3. Endothelin-converting enzyme 2 regulates κ opioid receptor trafficking and function.The Journal of pharmacology and experimental therapeutics · 2025
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  15. Luminal ANG II is internalized as a complex with ATAmerican journal of physiology. Renal physiology · 2017
    Article
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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

8 authors at 4 institutions in 2 countries.

Gyöngyi SzakadátiDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
András D TóthDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
Ilona OláhDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
László Sándor ErdélyiDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
Tamas BallaDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
Péter VárnaiDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
László HunyadyDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.) Hunyady@eok.sote.hu.
András BallaDepartment of Physiology, Semmelweis University, Faculty of Medicine, Budapest, Hungary (G.S., A.D.T., I.O., L.S.E., P.V., L.H., A.B.), Magyar Tudományos Akadémia-Semmelweis Egyetem Laboratory of Molecular Physiology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary (L.S.E., P.V., L.H., A.B.); and Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (T.B.).
Hungarian Academy of Sciences · HUEunice Kennedy Shriver National Institute of Child Health and Human Development · USSemmelweis University · HUNational Institutes of Health · US

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

Biased agonism on the type I angiotensin receptor (AT1-R) can achieve different outcomes via activation of G protein-dependent and -independent cellular responses. In this study, we investigated whether the biased activation of AT1-R can lead to different regulation and intracellular processing of the receptor. We analyzed β-arrestin binding, endocytosis, and subsequent trafficking steps, such as early and late phases of recycling of AT1-R in human embryonic kidney 293 cells expressing wild-type or biased mutant receptors in response to different ligands. We used Renilla luciferase-tagged receptors and yellow fluorescent protein-tagged β-arrestin2, Rab5, Rab7, and Rab11 proteins in bioluminescence resonance energy transfer measurements to follow the fate of the receptor after stimulation. We found that not only is the signaling of the receptor different upon using selective ligands, but the fate within the cells is also determined by the type of the stimulation. β-arrestin binding and the internalization kinetics of the angiotensin II-stimulated AT1-R differed from those stimulated by the biased agonists. Similarly, angiotensin II-stimulated wild-type AT1-R showed differences compared with a biased mutant AT1-R (DRY/AAY AT1-R) with regards to β-arrestin binding and endocytosis. We found that the differences in the internalization kinetics of the receptor in response to biased agonist stimulation are due to the differences in plasma membrane phosphatidylinositol 4,5-bisphosphate depletion. Moreover, the stability of the β-arrestin binding is a major determinant of the later fate of the internalized AT1-R receptor.

Indexed as

1-Phosphatidylinositol 4-KinaseAngiotensin IIArrestinsbeta-ArrestinsBioluminescence Resonance Energy Transfer TechniquesCell MembraneEndocytosisGreen Fluorescent ProteinsGTP-Binding Protein alpha Subunits, Gq-G11HEK293 CellsHumansHydrolysisLigandsLuciferases, RenillaPhosphatidylinositol 4,5-DiphosphatePhosphoinositide-3 Kinase Inhibitors1-Phosphatidylinositol 4-KinaseAngiotensin IIArrestinsbeta-Arrestinsenhanced green fluorescent proteinGreen Fluorescent ProteinsGTP-Binding Protein alpha Subunits, Gq-G11LigandsLuciferases, RenillaPhosphatidylinositol 4,5-DiphosphatePhosphoinositide-3 Kinase InhibitorsPhosphoinositide Phospholipase CReceptor, Angiotensin, Type 1

Identifiers

PMID25804845
PMCPMC4429721
OpenAlexW1989038441

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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.