ArticleThe Journal of biological chemistry2009
Epitope-tagged receptor knock-in mice reveal that differential desensitization of alpha2-adrenergic responses is because of ligand-selective internalization.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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.
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Identification of Catecholamine and Drug Target αJournal of clinical medicine · 2024Article
- Knock-In Mouse Models to Investigate the Functions of Opioid ReceptorsFrontiers in cellular neuroscience · 2022Review
- BiasNet: A Model to Predict Ligand Bias Toward GPCR Signaling.Journal of chemical information and modeling · 2021Article
- An N-terminal fusion allele to study melanin concentrating hormone receptor 1.Genesis (New York, N.Y. : 2000) · 2021Article
- Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles.Endocrinology · 2020Article
- In vivo mapping of a GPCR interactome using knockin mice.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade.Science translational medicine · 2020Article
- The in vivo specificity of synaptic Gβ and Gγ subunits to the αScientific reports · 2019Article
- Strategy for Identification of Phosphorylation Levels of Low Abundance Proteins in Vivo for Which Antibodies Are not Available.Journal of cardiovascular development and disease · 2017Article
- The amyloid precursor protein modulates αFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Desensitized D2 autoreceptors are resistant to trafficking.Scientific reports · 2017Article
- Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion.Experimental neurology · 2017Article
- Diverse arrestin-recruiting and endocytic profiles of tricyclic antipsychotics acting as direct αNeuropharmacology · 2017Article
- Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex.The European journal of neuroscience · 2014Article
- α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Cross-talk from β-adrenergic receptors modulates α2A-adrenergic receptor endocytosis in sympathetic neurons via protein kinase A and spinophilin.The Journal of biological chemistry · 2013Article
- Article
- Are the pharmacology and physiology of α₂ adrenoceptors determined by α₂-heteroreceptors and autoreceptors respectively?British journal of pharmacology · 2012Review
- The antidepressant desipramine is an arrestin-biased ligand at the α(2A)-adrenergic receptor driving receptor down-regulation in vitro and in vivo.The Journal of biological chemistry · 2011Article
- Therapeutic potential of β-arrestin- and G protein-biased agonists.Trends in molecular medicine · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Although ligand-selective regulation of G protein-coupled receptor-mediated signaling and trafficking are well documented, little is known about whether ligand-selective effects occur on endogenous receptors or whether such effects modify the signaling response in physiologically relevant cells. Using a gene targeting approach, we generated a knock-in mouse line, in which N-terminal hemagglutinin epitope-tagged alpha(2A)-adrenergic receptor (AR) expression was driven by the endogenous mouse alpha(2A)AR gene locus. Exploiting this mouse line, we evaluated alpha(2A)AR trafficking and alpha(2A)AR-mediated inhibition of Ca(2+) currents in native sympathetic neurons in response to clonidine and guanfacine, two drugs used for treatment of hypertension, attention deficit and hyperactivity disorder, and enhancement of analgesia through actions on the alpha(2A)AR subtype. We discovered a more rapid desensitization of Ca(2+) current suppression by clonidine than guanfacine, which paralleled a more marked receptor phosphorylation and endocytosis of alpha(2A)AR evoked by clonidine than by guanfacine. Clonidine-induced alpha(2A)AR desensitization, but not receptor phosphorylation, was attenuated by blockade of endocytosis with concanavalin A, indicating a critical role for internalization of alpha(2A)AR in desensitization to this ligand. Our data on endogenous receptor-mediated signaling and trafficking in native cells reveal not only differential regulation of G protein-coupled receptor endocytosis by different ligands, but also a differential contribution of receptor endocytosis to signaling desensitization. Taken together, our data suggest that these HA-alpha(2A)AR knock-in mice will serve as an important model in developing ligands to favor endocytosis or nonendocytosis of receptors, depending on the target cell and pathophysiology being addressed.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.