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BioAssay: AID 624203

Summary of the probe development efforts to identify agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A)

Name: Summary of the probe development efforts to identify agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A). ..more
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AID: 624203
Data Source: The Scripps Research Institute Molecular Screening Center (HTR2A_ACT_SUMMARY)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2012-05-24
Modify Date: 2012-08-20
Target
Related Experiments
AIDNameTypeComment
624169Luminescence-based cell-based primary high throughput screening assay to identify agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A)Screeningdepositor-specified cross reference: Primary screen (Htr2a agonists in singlicate)
624380Counterscreen for agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A): Luminescence-based cell-based high throughput screening assay to identify agonists of the mu 1 opioid receptor (OPRM1)Screeningdepositor-specified cross reference: Counterscreen (OPRM1 agonists in triplicate)
624381Luminescence-based cell-based high throughput confirmation assay for agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A)Screeningdepositor-specified cross reference: Confirmation assay (Htr2a agonists in triplicate)
624499Counterscreen for agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A): Luminescence-based cell-based high throughput dose response assay to identify agonists of the mu 1 opioid receptor (OPRM1)Confirmatorydepositor-specified cross reference: Dose response counterscreen (OPRM1 agonists in triplicate)
624503Luminescence-based cell-based high throughput dose response assay for agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A)Confirmatorydepositor-specified cross reference: Dose response assay (Htr2a agonists in triplicate)
720642On Hold
720643On Hold
Description:
Source (MLPCN Center Name): The Scripps Research Institute Molecular Screening Center (SRIMSC)
Affiliation: The Scripps Research Institute, TSRI
Assay Provider: Laura Bohn
Network: Molecular Library Probe Production Centers Network (MLPCN)
Grant Proposal Number: DA025158-01A1
Grant Proposal PI: Laura Bohn
External Assay ID: HTR2A_ACT_SUMMARY

Name: Summary of the probe development efforts to identify agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A).

Description:

Serotonin (5-hydroxytryptamine; 5-HT) is an abundant neurotransmitter synthesized from the essential amino acid L-tryptophan and plays a significant role in appetite, platelet aggregation, pain perception, sleep, hormone secretion, sexual behavior, and thermoregulation. Serotonin mediates much of its actions by binding to and activating G protein-coupled receptors (GPCR) on the surface of neurons and other cells. One of these GPCRs, the serotonin 2A receptor (5-HT2AR), is a 7-transmembrane spanning GPCR in the frontal cortex which impacts on development, anxiety, depression, perception, and cognitive function [1, 2]. In neurons, the 5-HT2AR is a constitutively internalizing receptor and this trafficking is dependent upon interactions with the regulatory protein, B-arrestin2 [3]. Studies in cell-based assays reveal that serotonin requires B-arrestin2 to internalize the receptors while other agonists, such as DOI, 5-MeO-DMT, and quipazine, internalize the receptor in the absence of B-arrestins [3, 4]. All 5-HT2AR agonists seem to recruit B-arrestin2 to 5-HT2AR in cultured cells. However, while serotonin requires B-arrestins to traffic receptors, other agonists such as DOI, 5-MeO-DMT, and quipazine can internalize the receptor in the absence of B-arrestins [3, 4]. It remains to be determined if the specific 5-HT2AR-B-arrestin interactions and trafficking events have physiological significance. It is conceivable that the regulation of 5-HT2AR in vivo may impact neurological sensitivity to serotonin and the responsiveness to pharmacological agents and drugs of abuse. We predict that drugs that disrupt the serotonin 2A receptor-B-arrestin interaction might provide a means to alter the sensitivity of the receptor to the levels of serotonin present in the brain[4]. These findings may inspire the development of drugs that could be clinically useful for treating depression, schizophrenia, and drug addiction [5-7].

Summary of Probe Development Effort:

This probe development effort is focused on the identification of agonists of the mouse 5-hydroxytryptamine (serotonin) receptor 2A (HTR2A). All AIDs that contain results associated with this project can be found in the "Related Bioassays" section of this Summary AID.

References:

1. Hsieh, C.L., A.M. Bowcock, L.A. Farrer, J.M. Hebert, K.N. Huang, L.L. Cavalli-Sforza, D. Julius, and U. Francke, The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14. Somat Cell Mol Genet, 1990. 16(6): p. 567-74.
2. Berger, M., J.A. Gray, and B.L. Roth, The expanded biology of serotonin. Annu Rev Med, 2009. 60: p. 355-66.
3. Schmid, C.L., K.M. Raehal, and L.M. Bohn, Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo. Proc Natl Acad Sci U S A, 2008. 105(3): p. 1079-84.
4. Bohn, L.M. and C.L. Schmid, Serotonin receptor signaling and regulation via beta-arrestins. Crit Rev Biochem Mol Biol, 2010. 45(6): p. 555-66.
5. Allen, J.A., P.N. Yadav, and B.L. Roth, Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases. Neuropharmacology, 2008. 55(6): p. 961-8.
6. Raehal, K.M. and L.M. Bohn, The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology, 2011. 60(1): p. 58-65.
7. Bohn, L.M. and P.H. McDonald, Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery. Drug Discov Today Technol, 2010. 7(1): p. e37-e42.

Keywords:

Summary, Summary AID, 5HT2AR, 5-HT2AR, Htr2a, HTR2A, 5-HT-2, 5-HT-2A, 5-HT2A receptor, 5-hydroxytryptamine 2 receptor, 5-hydroxytryptamine receptor 2A, serotonin receptor 2A, mouse, Mus musculus, agonist, serotonin, mimetic, ligand, GPCR, receptor, G-protein, Gi/Go, DiscoverRx, PathHunter, complementation, reconstitution, enzyme, beta-gal, beta-galactosidase, luminescence, lumi, cell-based, U2OS, endocytosis, fusion protein, enzyme fragment complementation, EFC, ProLink, activate, activator, activation, mood, depression, anxiety, pain, appetite, schizophrenia, HTS, high throughput screen, 1536, Scripps, Scripps Florida, MLSMR, The Scripps Research Institute Molecular Screening Center, SRIMSC, Molecular Libraries Probe Production Centers Network, MLPCN.
Additional Information
Grant Number: DA025158-01A1

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