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 language | English (US) |
|---|---|
| Pages (from-to) | 441-451 |
| Number of pages | 11 |
| Journal | Brain Research Bulletin |
| Volume | 56 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 15 2001 |
| Externally published | Yes |
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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 journal › Article
}
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 -