5-HT7 receptor
| HTR7 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process |
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| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) |
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| RefSeq (protein) |
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| Location (UCSC) | Chr 10: 90.74 – 90.86 Mb | Chr 19: 35.94 – 36.03 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
The 5-HT7 receptor is a member of the
Function
When the 5-HT7 receptor is activated by serotonin, it sets off a cascade of events starting with release of the stimulatory
The 5-HT7 receptor plays a role in
Variants
Three splice variants have been identified in humans (designated h5-HT7(a), h5-HT7(b), and h5-HT7(d)), which encode receptors that differ in their carboxy terminals.[9] The h5-HT7(a) is the full length receptor (445 amino acids),[7] while the h5-HT7(b) is truncated at amino acid 432 due to alternative splice donor site. The h5-HT7(d) is a distinct isoform of the receptor: the retention of an exon cassette in the region encoding the carboxyl terminal results a 479-amino acid receptor with a c-terminus markedly different from the h5-HT7(a). A 5-HT7(c) splice variant is detectable in rat tissue but is not expressed in humans. Conversely, rats do not express a splice variant homologous to the h5-HT7(d), as the rat 5-HT7 gene lacks the exon necessary to encode this isoform.[9] Drug binding affinities are similar across the three human splice variants;[13] however, inverse agonist efficacies appear to differ between the splice variants.[14]
Discovery
In 1983, evidence for a
Ligands
Numerous orthosteric ligands of moderate to high affinity are known. Signaling biased ligands were discovered and developed in 2018.[17]
Agonists
- 5-Carboxamidotryptamine (5-CT)
- 5-methoxytryptamine(5-MT, 5-MeOT)
- 8-OH-DPAT (mixed 5-HT1A/5-HT7 agonist)[18]
- Aripiprazole (weak partial agonist)[19]
- AS-19
- E-55888[20]
- E-57431[21]
- LP-12 (4-(2-Diphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide)
- LP-44 (4-[2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide)
- LP-211
- MSD-5a[22]
- Nω-Methylserotonin[23]
- N-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides (can function as either an agonist or antagonist depending on side chain substitution)[24][25]
- N,N-Dimethyltryptamine
- AGH-107 (water-soluble, brain penetrating full agonist) [26]
- AH-494 (3-(1-ethyl-1H-imidazol-5-yl)-1H-indole-5-carboxamide) [27]
- AGH-192 (orally bioavailable, water-soluble, brain penetrating full agonist)[28]
Antagonists
- 3-{4-[4-(4-chlorophenyl)-piperazin-1-yl]-butyl}-3-ethyl-6-fluoro-1,3-dihydro-2H-indol-2-one[31]
- Amisulpride[32]
- Amitriptyline
- Amoxapine
- Brexpiprazole
- Clomipramine
- Clozapine
- CYY1005 (a highly selective, orally active 5-HT7 antagonist) [10]
- DR-4485
- EGIS-12233(mixed 5-HT6/5-HT7 antagonist)
- AVN-101 (mixed 5-HT6/5-HT7 antagonist) [33]
- Fluphenazine
- Fluperlapine
- ICI 169,369
- Imipramine
- JNJ-18038683
- Ketanserin
- Loxapine
- Lurasidone
- LY-215,840
- Maprotiline
- Mesulergine
- Methysergide
- Mianserin
- Olanzapine
- Pimozide
- RA-7 (1-(2-diphenyl)piperazine)[34]
- Ritanserin
- SB-258741[37]
- SB-269970 (highly 5-HT7 selective)[38]
- SB-656104-A[39]
- SB-691673[35]
- Sertindole
- Spiperone
- Tenilapine
- TFMPP
- Vortioxetine
- Trifluoperazine
- Ziprasidone
- Zotepine
Inactivating antagonists
Inactivating antagonists are non-competitive antagonists that render the receptor persistently insensitive to agonist, which resembles receptor desensitization. Inactivation of the 5-HT7 receptor, however, does not arise from the classically described mechanisms of receptor desensitization via receptor phosphorylation, beta-arrestin recruitment, and receptor internalization.[40] Inactivating antagonists all likely interact with the 5-HT7 receptor in an irreversible/pseudo-irreversible manner, as is the case with [3H]risperidone.[41][42]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000148680 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024798 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 10664612.
- PMID 8397408.
- ^ PMID 8226867.
- PMID 18301795.
- ^ S2CID 25951920.
- ^ PMID 35585132.
- PMID 15559250.
- PMID 24935787.
- S2CID 21899516.
- ^ PMID 11906971.
- PMID 6662198.
- S2CID 25543069.
- S2CID 51700960.
- S2CID 41623573.
- ^ Davies MA, Sheffler DJ, Roth BL. Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology. CNS Drug Reviews [Internet]. 2004 [cited 2013 Aug 4];10(4):317–36. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00030.x/pdf
- PMID 21778664.
- S2CID 16613426.
- S2CID 27144262.
- PMID 19049296.
- PMID 17649988.
- PMID 15588097.
- PMID 28473721.
- PMID 30568756.
- S2CID 85498356.
- PMID 17897083.
- PMID 15032609.
- PMID 18361484.
- PMID 19337725.
- PMID 27232215.
- PMID 22738316.
- ^ S2CID 25203956.
- PMID 9513592.
- ^ PMID 15249157.
- PMID 10669560.
- PMID 12392747.
- PMID 9606723.
- ^ S2CID 1678887.
- ^ PMID 18996971.
External links
- "5-HT7". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Human HTR7 genome location and HTR7 gene details page in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.