Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists

  title={Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists},
  author={John A. Gray and Bryan L. Roth},
  journal={Brain Research Bulletin},
  • J. A. GrayB. Roth
  • Published 15 November 2001
  • Biology, Psychology
  • Brain Research Bulletin


The results suggest an indispensible role for scaffolding proteins and kinases in normal 5-HT 2A trafficking, targeting, trafficking and signaling in normal 4- HT 2A signaling and signaling.

Serotonin receptors involved in antidepressant effects.

  • F. Artigas
  • Biology, Psychology
    Pharmacology & therapeutics
  • 2013

Agonist-directed signaling of the serotonin 2A receptor depends on β-arrestin-2 interactions in vivo

This study suggests that the 5-HT2AR–β-arrestin interaction may be particularly important in receptor function in response to endogenous serotonin levels, which could have major implications in drug development for treating neuropsychiatric disorders such as depression and schizophrenia.

Central serotonin-2A (5-HT2A) receptor dysfunction in depression and epilepsy: the missing link?

How these receptors may directly or indirectly control neuronal excitability in most networks involved in depression and epilepsy through interactions with the monoaminergic, GABAergic and glutamatergic neurotransmissions is illustrated.

Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization.

The findings indicate that the process of agonist-mediated desensitization of 5-HT(2A) receptors requires the presence of two nonconserved serine residues located in distinct intracellular loops.

Differential regulation of rat peripheral 5-HT2A and 5-HT2B receptor systems: influence of drug treatment

It is suggested that regulation of peripheral 5-HT2 receptors (5-HT 2A and 5- HT2B) is a functionally significant phenomenon in vivo, and occurs after administration of both agonists and antagonists.

The therapeutic role of 5-HT1A and 5-HT2A receptors in depression.

The prevention of a negative feedback mechanism operating at the 5-HT autoreceptor level enhances the neurochemical and clinical effects of SSRIs, and the blockade of 5- HT2A receptors also seems to improve theclinical effects ofSSRIs.



5‐HT2 Receptors, Roles and Regulation

5-HT2 receptors labeled by an antagonist and an agonist ligand were similarly decreased and vascular smooth muscle cells in culture kept for at least 24 h in a serotonin-free medium were rapidly desensitized.

Regulation of 5-HT2 and 5-HT1C serotonin receptor levels. Methodology and mechanisms.

  • B. RothM. HamblinR. Ciaranello
  • Biology, Psychology
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1990
Preliminary information suggests that developmentally induced alterations in 5-HT2 and5-HT1c receptors may be due to transcriptional regulation while changes caused by mianserin treatment might bedue to posttranslational processes.

Effects of agonists, partial agonists, and antagonists on the regulation of 5-hydroxytryptamine2 receptors in P11 cells.

The ability of ketanserin and mianserin to down-regulate receptors in vivo is the result of indirect actions of these drugs and is unlikely to be a direct consequence of receptor occupancy by antagonists.

Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation.

An integrated model of 5-HT2A receptor regulation that involves various protein kinases (protein kinase C, G-protein receptor kinases, arrestins, clathrin-coated vesicles, endosomes and lysosomes) and the relevance of these pathways for antidepressant and antipsychotic drug actions is emphasized.

Antagonist-mediated down-regulation of 5-hydroxytryptamine type 2 receptor gene expression: modulation of transcription.

It is shown that long term treatment with serotonin or mianserin, an antagonist and antidepressant, results in reduced levels of both the 5-HT2 receptor and its RNA.

Gaps and peculiarities in 5-HT2 receptor studies.

  • J. Leysen
  • Biology
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1990
It is argued that apparent differences in the occurrence and density of 5-HT2 receptors labeled with radioactive agonists and antagonists may be due to tissue preparation and assay conditions, and the hypothesis that 5- HT2 receptors probably receive little stimulation under normal physiologic conditions, could provide an explanation for various anomalous findings.

Rapid desensitization and down-regulation of 5-HT2 receptors by DOM treatment.

Distinct Mechanisms Regulate 5-HT2 and Thrombin Receptor Desensitization (*)

Both 5-HT2 and thrombin receptors have unique shut-off mechanisms, and sequences in the carboxyl terminus of the throm bin receptor are sufficient to trigger rapid uncoupling of the receptor from its G protein(s) and downstream effector(s).