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

John Gray, Bryan L. Roth

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

5-Hydroxytryptamine2A (serotonin2A, 5-HT2A) receptors are important for many physiologic processes including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. A large number of pharmaceutical agents mediate their actions, at least in part, by modulating the number and/or activity of 5-HT2A receptors. Drugs with action at 5-HT2A receptors are used in the treatment of many disorders, including schizophrenia, depression, and anxiety disorders. This review summarizes over two decades of research on the regulation of 5-HT2A receptors and provides a comprehensive review of numerous in vivo studies describing the paradoxical phenomenon of 5-HT2A receptor down-regulation by chronic treatment with antidepressants and antipsychotics. In addition, studies reporting antagonist-induced internalization of 5-HT2A receptors and other G protein-coupled receptors will be highlighted as a possible mechanism to explain this paradoxical down-regulation. Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT2A receptors will be presented.

Original languageEnglish (US)
Pages (from-to)441-451
Number of pages11
JournalBrain Research Bulletin
Volume56
Issue number5
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

Fingerprint

Serotonin 5-HT2 Receptor Agonists
Serotonin 5-HT2 Receptor Antagonists
Receptor, Serotonin, 5-HT2A
Down-Regulation
Muscle Contraction
G-Protein-Coupled Receptors
Anxiety Disorders
Platelet Aggregation
Pharmaceutical Preparations
Antidepressive Agents
Antipsychotic Agents
Smooth Muscle
Schizophrenia
Depression

Keywords

  • Antidepressant
  • Antipsychotic
  • Arrestin
  • Clozapine
  • Down-regulation
  • Internalization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists. / Gray, John; Roth, Bryan L.

In: Brain Research Bulletin, Vol. 56, No. 5, 15.11.2001, p. 441-451.

Research output: Contribution to journalArticle

@article{33454ae28d8347f0a26005632ba8ee5a,
title = "Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists",
abstract = "5-Hydroxytryptamine2A (serotonin2A, 5-HT2A) receptors are important for many physiologic processes including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. A large number of pharmaceutical agents mediate their actions, at least in part, by modulating the number and/or activity of 5-HT2A receptors. Drugs with action at 5-HT2A receptors are used in the treatment of many disorders, including schizophrenia, depression, and anxiety disorders. This review summarizes over two decades of research on the regulation of 5-HT2A receptors and provides a comprehensive review of numerous in vivo studies describing the paradoxical phenomenon of 5-HT2A receptor down-regulation by chronic treatment with antidepressants and antipsychotics. In addition, studies reporting antagonist-induced internalization of 5-HT2A receptors and other G protein-coupled receptors will be highlighted as a possible mechanism to explain this paradoxical down-regulation. Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT2A receptors will be presented.",
keywords = "Antidepressant, Antipsychotic, Arrestin, Clozapine, Down-regulation, Internalization",
author = "John Gray and Roth, {Bryan L.}",
year = "2001",
month = "11",
day = "15",
doi = "10.1016/S0361-9230(01)00623-2",
language = "English (US)",
volume = "56",
pages = "441--451",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists

AU - Gray, John

AU - Roth, Bryan L.

PY - 2001/11/15

Y1 - 2001/11/15

N2 - 5-Hydroxytryptamine2A (serotonin2A, 5-HT2A) receptors are important for many physiologic processes including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. A large number of pharmaceutical agents mediate their actions, at least in part, by modulating the number and/or activity of 5-HT2A receptors. Drugs with action at 5-HT2A receptors are used in the treatment of many disorders, including schizophrenia, depression, and anxiety disorders. This review summarizes over two decades of research on the regulation of 5-HT2A receptors and provides a comprehensive review of numerous in vivo studies describing the paradoxical phenomenon of 5-HT2A receptor down-regulation by chronic treatment with antidepressants and antipsychotics. In addition, studies reporting antagonist-induced internalization of 5-HT2A receptors and other G protein-coupled receptors will be highlighted as a possible mechanism to explain this paradoxical down-regulation. Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT2A receptors will be presented.

AB - 5-Hydroxytryptamine2A (serotonin2A, 5-HT2A) receptors are important for many physiologic processes including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. A large number of pharmaceutical agents mediate their actions, at least in part, by modulating the number and/or activity of 5-HT2A receptors. Drugs with action at 5-HT2A receptors are used in the treatment of many disorders, including schizophrenia, depression, and anxiety disorders. This review summarizes over two decades of research on the regulation of 5-HT2A receptors and provides a comprehensive review of numerous in vivo studies describing the paradoxical phenomenon of 5-HT2A receptor down-regulation by chronic treatment with antidepressants and antipsychotics. In addition, studies reporting antagonist-induced internalization of 5-HT2A receptors and other G protein-coupled receptors will be highlighted as a possible mechanism to explain this paradoxical down-regulation. Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT2A receptors will be presented.

KW - Antidepressant

KW - Antipsychotic

KW - Arrestin

KW - Clozapine

KW - Down-regulation

KW - Internalization

UR - http://www.scopus.com/inward/record.url?scp=0035891883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035891883&partnerID=8YFLogxK

U2 - 10.1016/S0361-9230(01)00623-2

DO - 10.1016/S0361-9230(01)00623-2

M3 - Article

C2 - 11750789

AN - SCOPUS:0035891883

VL - 56

SP - 441

EP - 451

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

IS - 5

ER -