5-HT7 receptor: Difference between revisions

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{{Wrongtitle|title=5-HT<sub>7</sub> receptor}}
{{DISPLAYTITLE:5-HT<sub>7</sub> receptor}}
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{{Infobox_gene}}
{{PBB_Controls
| update_page = yes
The '''5-HT<sub>7</sub> receptor''' is a member of the [[G-protein coupled receptor|GPCR]] superfamily of cell surface [[receptor (biochemistry)|receptors]] and is activated by the [[neurotransmitter]] [[serotonin]] (5-hydroxytryptamine, 5-HT)<ref name="pmid10664612">{{cite journal | vauthors = Vanhoenacker P, Haegeman G, Leysen JE | title = 5-HT7 receptors: current knowledge and future prospects | journal = Trends in Pharmacological Sciences | volume = 21 | issue = 2 | pages = 70–7 | date = February 2000 | pmid = 10664612 | doi = 10.1016/S0165-6147(99)01432-7 }}</ref> The 5-HT<sub>7</sub> receptor is coupled to [[Heterotrimeric G protein|G<sub>s</sub>]] (stimulates the production of the intracellular signaling molecule [[Cyclic adenosine monophosphate|cAMP]])<ref name="pmid8397408">{{cite journal | vauthors = Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC | title = Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 18 | pages = 8547–51 | date = September 1993 | pmid = 8397408 | pmc = 47394 | doi = 10.1073/pnas.90.18.8547 }}</ref><ref name="pmid8226867">{{cite journal | vauthors = Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL | title = Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase | journal = The Journal of Biological Chemistry | volume = 268 | issue = 31 | pages = 23422–6 | date = November 1993 | pmid = 8226867 | doi =  }}</ref> and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels.<ref name="pmid8226867"/> This receptor has been a drug development target for the treatment of several clinical disorders.<ref name="pmid18301795">{{cite journal | vauthors = Mnie-Filali O, Lambás-Señas L, Zimmer L, Haddjeri N | title = 5-HT7 receptor antagonists as a new class of antidepressants | journal = Drug News & Perspectives | volume = 20 | issue = 10 | pages = 613–8 | date = December 2007 | pmid = 18301795 | doi = 10.1358/dnp.2007.20.10.1181354 }}</ref> The 5-HT<sub>7</sub> receptor is encoded by the ''HTR7'' [[gene]], which in humans is transcribed into 3 different splice variants.<ref name="pmid9084407">{{cite journal | vauthors = Heidmann DE, Metcalf MA, Kohen R, Hamblin MW | title = Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization | journal = Journal of Neurochemistry | volume = 68 | issue = 4 | pages = 1372–81 | date = April 1997 | pmid = 9084407 | doi = 10.1046/j.1471-4159.1997.68041372.x }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = 5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled)
| HGNCid = 5302
| Symbol = HTR7
| AltSymbols =; 5-HT7
| OMIM = 182137
| ECnumber = 
| Homologene = 20244
| MGIid = 99841
| GeneAtlas_image1 = PBB_GE_HTR7_207818_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_HTR7_216098_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_HTR7_207927_at_tn.png
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004977 |text = melanocortin receptor activity}} {{GNF_GO|id=GO:0004993 |text = serotonin receptor activity}}
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007187 |text = G-protein signaling, coupled to cyclic nucleotide second messenger}} {{GNF_GO|id=GO:0007268 |text = synaptic transmission}} {{GNF_GO|id=GO:0007623 |text = circadian rhythm}} {{GNF_GO|id=GO:0008015 |text = circulation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3363
    | Hs_Ensembl = ENSG00000148680
    | Hs_RefseqProtein = NP_000863
    | Hs_RefseqmRNA = NM_000872
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 10
    | Hs_GenLoc_start = 92490558
    | Hs_GenLoc_end = 92607651
    | Hs_Uniprot = P34969
    | Mm_EntrezGene = 15566
    | Mm_Ensembl = ENSMUSG00000024798
    | Mm_RefseqmRNA = NM_008315
    | Mm_RefseqProtein = NP_032341
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 36025416
    | Mm_GenLoc_end = 36122492
    | Mm_Uniprot = Q14A50
  }}
}}
'''5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled)''', also known as '''HTR7''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HTR7 5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3363| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
When the 5-HT<sub>7</sub> receptor is activated by serotonin, it sets off a cascade of events starting with release of the stimulatory [[heterotrimeric G protein|G protein]] [[Gs alpha subunit|G<sub>s</sub>]] from the GPCR complex. G<sub>s</sub> in turn activates [[adenylate cyclase]] which increases [[intracellular]] levels of the [[second messenger system|second messenger]] [[cyclic adenosine monophosphate|cAMP]].
{{PBB_Summary
| section_title =
| summary_text = The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends.<ref name="entrez">{{cite web | title = Entrez Gene: HTR7 5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3363| accessdate = }}</ref>
}}


==Ligands==
The 5-HT<sub>7</sub> receptor plays a role in [[smooth muscle]] [[muscle relaxant|relaxation]] within the [[vasculature]] and in the [[gastrointestinal tract]].<ref name="pmid10664612"/> The highest 5-HT<sub>7</sub> receptor densities are in the [[thalamus]] and [[hypothalamus]], and it is present at higher densities also in the [[hippocampus]] and [[Cerebral cortex|cortex]]. The 5-HT<sub>7</sub> receptor is involved in [[thermoregulation]], [[circadian rhythm]], [[learning]] and [[memory]], and [[sleep]]. It is also speculated that this receptor may be involved in [[Mood (psychology)|mood]] regulation, suggesting that it may be a useful target in the treatment of [[major depression|depression]].<ref name="pmid15559250">{{cite journal | vauthors = Hedlund PB, Sutcliffe JG | title = Functional, molecular and pharmacological advances in 5-HT7 receptor research | journal = Trends in Pharmacological Sciences | volume = 25 | issue = 9 | pages = 481–6 | date = September 2004 | pmid = 15559250 | doi = 10.1016/j.tips.2004.07.002 }}</ref><ref>{{cite journal | vauthors = Naumenko VS, Popova NK, Lacivita E, Leopoldo M, Ponimaskin EG | title = Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders | journal = CNS Neuroscience & Therapeutics | volume = 20 | issue = 7 | pages = 582–90 | date = July 2014 | pmid = 24935787 | doi = 10.1111/cns.12247 }}</ref>
There are several ligands that [[binding (molecular)|binds]] to the 5-HT<sub>7</sub> receptor
* ''N''-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides<ref name="pmid17649988">{{cite journal | author = Leopoldo M, Lacivita E, Contino M, Colabufo NA, Berardi F, Perrone R | title = Structure-activity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides, a class of 5-HT<sub>7</sub> receptor agents. 2 | journal = J. Med. Chem. | volume = 50 | issue = 17 | pages = 4214–21 | year = 2007 | pmid = 17649988 | doi = 10.1021/jm070487n | issn = }}</ref>
*[[8-OH-DPAT]] (5-HT<sub>1A/7</sub> [[agonist]])<ref name="pmid14654097">{{cite journal | author = Sprouse J, Reynolds L, Li X, Braselton J, Schmidt A | title = 8-OH-DPAT as a 5-HT<sub>7</sub> agonist: phase shifts of the circadian biological clock through increases in cAMP production | journal = Neuropharmacology | volume = 46 | issue = 1 | pages = 52–62 | year = 2004 | pmid = 14654097 | doi = 10.1016/j.neuropharm.2003.08.007 | issn = }}</ref>
* SB-269970 ([[antagonist]])<ref>{{Cite journal
| author = P. J. Lovell et al.
| title = A novel, potent, and selective 5-HT<sub>7</sub> antagonist : (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970)
| journal = [[Journal of Medicinal Chemistry]]
| year = 2000
| volume = 43
| issue = 3
| pages = 342&ndash;345
| pmid = 10669560
}}</ref>


==See also==
== Variants ==
 
Three [[alternative splicing|splice variants]] have been identified in humans (designated h5-HT<sub>7(a)</sub>, h5-HT<sub>7(b)</sub>, and h5-HT<sub>7(d)</sub>), which encode receptors that differ in their [[C-terminus|carboxy terminals]].<ref name="pmid9084407" /> The h5-HT<sub>7(a)</sub> is the full length receptor (445 amino acids),<ref name="pmid8226867"/> while the h5-HT<sub>7(b)</sub> is truncated at amino acid 432 due to alternative splice donor site. The h5-HT<sub>7(d)</sub> 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-HT<sub>7(a)</sub>. A 5-HT<sub>7(c)</sub> 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-HT<sub>7(d)</sub>, as the rat 5-HT<sub>7</sub> gene lacks the exon necessary to encode this isoform.<ref name="pmid9084407"/> Drug binding affinities are similar across the three human splice variants;<ref name="pmid11414657">{{cite journal | vauthors = Krobert KA, Bach T, Syversveen T, Kvingedal AM, Levy FO | title = The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 363 | issue = 6 | pages = 620–32 | date = June 2001 | pmid = 11414657 | doi = 10.1007/s002100000369 }}</ref> however, inverse agonist efficacies appear to differ between the splice variants.<ref name="pmid11906971">{{cite journal | vauthors = Krobert KA, Levy FO | title = The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects | journal = British Journal of Pharmacology | volume = 135 | issue = 6 | pages = 1563–71 | date = March 2002 | pmid = 11906971 | pmc = 1573253 | doi = 10.1038/sj.bjp.0704588 }}</ref>
 
== Discovery ==
 
In 1983, evidence for a [[5-HT1|5-HT<sub>1</sub>]]-like receptor was first found.<ref>{{cite journal | vauthors = Feniuk W, Humphrey PP, Watts AD | title = 5-Hydroxytryptamine-induced relaxation of isolated mammalian smooth muscle | journal = European Journal of Pharmacology | volume = 96 | issue = 1–2 | pages = 71–8 | date = December 1983 | pmid = 6662198 | doi = 10.1016/0014-2999(83)90530-7 }}</ref> Ten years later, 5-HT<sub>7</sub> receptor was cloned and characterized.<ref name="pmid8226867" /> It has since become clear that the receptor described in 1983 is 5-HT<sub>7</sub>.<ref>{{cite journal | vauthors = Hoyer D, Hannon JP, Martin GR | title = Molecular, pharmacological and functional diversity of 5-HT receptors | journal = Pharmacology Biochemistry and Behavior | volume = 71 | issue = 4 | pages = 533–54 | date = April 2002 | pmid = 11888546 | doi = 10.1016/S0091-3057(01)00746-8 }}</ref>
 
== Clinical significance ==
 
This receptor gene is a candidate [[gene locus|locus]] for involvement in [[autism]] and other neuropsychiatric conditions.<ref name="pmid10490701">{{cite journal | vauthors = Lassig JP, Vachirasomtoon K, Hartzell K, Leventhal M, Courchesne E, Courchesne R, Lord C, Leventhal BL, Cook EH | title = Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder | journal = American Journal of Medical Genetics | volume = 88 | issue = 5 | pages = 472–5 | date = October 1999 | pmid = 10490701 | doi = 10.1002/(SICI)1096-8628(19991015)88:5<472::AID-AJMG7>3.0.CO;2-G }}</ref>
 
== Ligands ==
 
Numerous orthosteric ligands of moderate to high affinity are known. [[Functional selectivity|Signaling biased ligands]] were discovered and developed in 2018.<ref name="pmid30028132">{{cite journal |vauthors=Kim Y, Kim H, Lee J, Lee JK, Min SJ, Seong J, Rhim H, Tae J, Lee HJ, Choo H |title=Discovery of β-Arrestin Biased Ligands of 5-HT7R |journal=J. Med. Chem. |volume= 61|issue= 16|pages= 7218–7233|date=August 2018 |pmid=30028132 |doi=10.1021/acs.jmedchem.8b00642 |url=}}</ref>
 
=== Agonists ===
 
[[Agonists]] mimic the effects of the endogenous ligand, which is serotonin at the 5-HT<sub>7</sub> receptor (↑cAMP).
{{Div col|colwidth=30em}}
* [[5-Carboxamidotryptamine]] (5-CT)
* [[5-methoxytryptamine]] (5-MT, 5-MeOT)
* [[8-OH-DPAT]] (mixed [[5-HT1A receptor|5-HT<sub>1A</sub>]]/5-HT<sub>7</sub> agonist)<ref name="pmid14654097">{{cite journal | vauthors = Sprouse J, Reynolds L, Li X, Braselton J, Schmidt A | title = 8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock through increases in cAMP production | journal = Neuropharmacology | volume = 46 | issue = 1 | pages = 52–62 | date = January 2004 | pmid = 14654097 | doi = 10.1016/j.neuropharm.2003.08.007 }}</ref>
* [[Aripiprazole]] (weak [[partial agonist]])<ref>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</ref>
* [[AS-19 (drug)|AS-19]]
* [[E-55888]]<ref name="pmid21778664">{{cite journal | vauthors = Brenchat A, Ejarque M, Zamanillo D, Vela JM, Romero L | title = Potentiation of morphine analgesia by adjuvant activation of 5-HT7 receptors | journal = Journal of Pharmacological Sciences | volume = 116 | issue = 4 | pages = 388–91 | date = August 2011 | pmid = 21778664 | doi = 10.1254/jphs.11039sc }}</ref>
* [[E-57431]]<ref name="pmid20399562">{{cite journal | vauthors = Brenchat A, Nadal X, Romero L, Ovalle S, Muro A, Sánchez-Arroyos R, Portillo-Salido E, Pujol M, Montero A, Codony X, Burgueño J, Zamanillo D, Hamon M, Maldonado R, Vela JM | title = Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity | journal = Pain | volume = 149 | issue = 3 | pages = 483–94 | date = June 2010 | pmid = 20399562 | doi = 10.1016/j.pain.2010.03.007 }}</ref>
* [[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]]<ref name="pmid19118950">{{cite journal | vauthors = Brenchat A, Romero L, García M, Pujol M, Burgueño J, Torrens A, Hamon M, Baeyens JM, Buschmann H, Zamanillo D, Vela JM | title = 5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice | journal = Pain | volume = 141 | issue = 3 | pages = 239–47 | date = February 2009 | pmid = 19118950 | doi = 10.1016/j.pain.2008.11.009 }}</ref>
* [[N-Methylserotonin|''N<sub>ω</sub>''-Methylserotonin]]<ref name="Powell et al.">{{cite journal | vauthors = Powell SL, Gödecke T, Nikolic D, Chen SN, Ahn S, Dietz B, Farnsworth NR, van Breemen RB, Lankin DC, Pauli GF, Bolton JL | title = In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 24 | pages = 11718–26 | date = December 2008 | pmid = 19049296 | pmc = 3684073 | doi = 10.1021/jf803298z }}</ref>
* ''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)<ref name="pmid17649988">{{cite journal | vauthors = Leopoldo M, Lacivita E, Contino M, Colabufo NA, Berardi F, Perrone R | title = Structure-activity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides, a class of 5-HT7 receptor agents. 2 | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 17 | pages = 4214–21 | date = August 2007 | pmid = 17649988 | doi = 10.1021/jm070487n }}</ref><ref name="pmid15588097">{{cite journal | vauthors = Leopoldo M, Berardi F, Colabufo NA, Contino M, Lacivita E, Niso M, Perrone R, Tortorella V | title = Structure-affinity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides, a new class of 5-hydroxytryptamine7 receptor agents | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 26 | pages = 6616–24 | date = December 2004 | pmid = 15588097 | doi = 10.1021/jm049702f }}</ref>
* [[N,N-Dimethyltryptamine]]
* [[1-(2-Diphenyl)piperazine|RA-7]] (1-(2-diphenyl)piperazine)
* [[AGH-107]] (3‐(1‐ethyl‐1H‐imidazol‐5‐yl)‐5‐iodo‐1H‐indole) <ref name="pmid28473721">{{cite journal | vauthors = Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, Latacz G, Handzlik J, Kieć-Kononowicz K, Wierońska JM, Woźniak M, Cieślik P, Bugno R, Staroń J, Bojarski AJ | title = Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol | journal = Scientific Reports | volume = 7 | pages = 1444 | number= 1444 | date = May 2017 | pmid = 28473721 | pmc = 5431432 | doi = 10.1038/s41598-017-00822-4 }}</ref>{{Div col end}}
 
=== Antagonists ===
 
[[receptor antagonist|Neutral antagonists]] (also known as silent antagonists) bind the receptor and have no [[Efficacy|intrinsic activity]] but will block the activity of agonists or inverse agonists. [[Inverse agonists]] inhibit the [[Receptor (biochemistry)#Constitutive activity|constitutive activity]] of the receptor, producing functional effects opposite to those of agonists (at the 5-HT<sub>7</sub> receptor: ↓cAMP).<ref name="pmid17897083">{{cite journal | vauthors = Pittalà V, Salerno L, Modica M, Siracusa MA, Romeo G | title = 5-HT7 receptor ligands: recent developments and potential therapeutic applications | journal = Mini Reviews in Medicinal Chemistry | volume = 7 | issue = 9 | pages = 945–60 | date = September 2007 | pmid = 17897083 | doi = 10.2174/138955707781662663 }}</ref><ref name="pmid15032609">{{cite journal | vauthors = Leopoldo M | title = Serotonin(7) receptors (5-HT(7)Rs) and their ligands | journal = Current Medicinal Chemistry | volume = 11 | issue = 5 | pages = 629–61 | date = March 2004 | pmid = 15032609 | doi = 10.2174/0929867043455828 }}</ref> Neutral antagonists and inverse agonists are typically referred to collectively as "antagonists" and, in the case of the 5-HT<sub>7</sub> receptor, differentiation between neutral antagonists and inverse agonists is problematic due to differing levels inverse agonist efficacy between receptor splice variants. For instance, mesulergine and metergoline are reported to be neutral antagonists at the h5-HT<sub>7(a)</sub> and h5-HT<sub>7(d)</sub> receptor isoforms but these drugs display marked inverse agonist effects at the h5-HT<sub>7(b)</sub> splice variant.<ref name="pmid11906971"/>
 
{{Div col|colwidth=30em}}
* 3-{4-[4-(4-chlorophenyl)-piperazin-1-yl]-butyl}-3-ethyl-6-fluoro-1,3-dihydro-2''H''-indol-2-one<ref name="pmid18361484">{{cite journal | vauthors = Volk B, Barkóczy J, Hegedus E, Udvari S, Gacsályi I, Mezei T, Pallagi K, Kompagne H, Lévay G, Egyed A, Hársing LG, Spedding M, Simig G | title = (Phenylpiperazinyl-butyl)oxindoles as selective 5-HT7 receptor antagonists | journal = Journal of Medicinal Chemistry | volume = 51 | issue = 8 | pages = 2522–32 | date = April 2008 | pmid = 18361484 | doi = 10.1021/jm070279v }}</ref>
* [[Amisulpride]]<ref name="pmid19337725">{{cite journal | vauthors = Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL | title = Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo | journal = Psychopharmacology | volume = 205 | issue = 1 | pages = 119–28 | date = July 2009 | pmid = 19337725 | pmc = 2821721 | doi = 10.1007/s00213-009-1521-8 }}</ref>
* [[Amitriptyline]]
* [[Amoxapine]]
* [[Clomipramine]]
* [[Clozapine]]
* [[DR-4485]]
* [[EGIS-12233]] (mixed 5-HT<sub>6</sub>/5-HT<sub>7</sub> antagonist)
* [[Fluphenazine]]
* [[Fluperlapine]]
* [[ICI 169,369]]
* [[Imipramine]]
* [[JNJ-18038683]]
* [[Ketanserin]]
* [[Loxapine]]
* [[Lurasidone]]
* [[LY-215,840]]
* [[Maprotiline]]
* [[Mesulergine]]
* [[Methysergide]]
* [[Mianserin]]
* [[Olanzapine]]
* [[Pimozide]]
* [[Ritanserin]]
* [[SB-258,719]]<ref name="pmid16967291"/><ref name="pmid9513592">{{cite journal | vauthors = Forbes IT, Dabbs S, Duckworth DM, Jennings AJ, King FD, Lovell PJ, Brown AM, Collin L, Hagan JJ, Middlemiss DN, Riley GJ, Thomas DR, Upton N | title = (R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl) propyl]benzenesulfonamide: the first selective 5-HT7 receptor antagonist | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 5 | pages = 655–7 | date = February 1998 | pmid = 9513592 | doi = 10.1021/jm970519e }}</ref><ref name="pmid15249157">{{cite journal | vauthors = Mahé C, Loetscher E, Feuerbach D, Müller W, Seiler MP, Schoeffter P | title = Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors | journal = European Journal of Pharmacology | volume = 495 | issue = 2–3 | pages = 97–102 | date = July 2004 | pmid = 15249157 | doi = 10.1016/j.ejphar.2004.05.033 }}</ref>
* [[SB-258741]]<ref name="pmid15249157"/>
* [[SB-269970]] (highly 5-HT<sub>7</sub> selective)<ref name="pmid10669560">{{cite journal | vauthors = Lovell PJ, Bromidge SM, Dabbs S, Duckworth DM, Forbes IT, Jennings AJ, King FD, Middlemiss DN, Rahman SK, Saunders DV, Collin LL, Hagan JJ, Riley GJ, Thomas DR | title = A novel, potent, and selective 5-HT(7) antagonist: (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl) phen ol (SB-269970) | journal = Journal of Medicinal Chemistry | volume = 43 | issue = 3 | pages = 342–5 | date = February 2000 | pmid = 10669560 | doi = 10.1021/jm991151j }}</ref>
* [[SB-656104-A]]<ref name="pmid12392747">{{cite journal | vauthors = Forbes IT, Douglas S, Gribble AD, Ife RJ, Lightfoot AP, Garner AE, Riley GJ, Jeffrey P, Stevens AJ, Stean TO, Thomas DR | title = SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties | journal = Bioorganic & Medicinal Chemistry Letters | volume = 12 | issue = 22 | pages = 3341–4 | date = November 2002 | pmid = 12392747 | doi = 10.1016/S0960-894X(02)00690-X }}</ref>
* [[SB-691673]]<ref name="pmid16967291">{{cite journal | vauthors = Romero G, Pujol M, Pauwels PJ | title = Reanalysis of constitutively active rat and human 5-HT7(a) receptors in HEK-293F cells demonstrates lack of silent properties for reported neutral antagonists | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 374 | issue = 1 | pages = 31–9 | date = October 2006 | pmid = 16967291 | doi = 10.1007/s00210-006-0093-y }}</ref>
* [[Sertindole]]
* [[Spiperone]]
* [[Tenilapine]]
* [[TFMPP]]
* [[Vortioxetine]]
* [[Trifluoperazine]]
* [[Ziprasidone]]
* [[Zotepine]]
{{Div col end}}
 
==== Inactivating antagonists ====
 
Inactivating antagonists are non-competitive antagonists that render the receptor persistently insensitive to agonist, which resembles receptor desensitization. Inactivation of the 5-HT<sub>7</sub> receptor, however, does not arise from the classically described mechanisms of receptor desensitization via receptor phosphorylation, beta-arrestin recruitment, and receptor internalization.<ref name="pmid9606723">{{cite journal | vauthors = Zhang J, Ferguson SS, Barak LS, Aber MJ, Giros B, Lefkowitz RJ, Caron MG | title = Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization | journal = Receptors & Channels | volume = 5 | issue = 3–4 | pages = 193–9 | year = 1997 | pmid = 9606723 }}</ref> Inactivating antagonists all likely interact with the 5-HT<sub>7</sub> receptor in an irreversible/pseudo-irreversible manner, as is the case with [<sup>3</sup>H]risperidone.<ref name="pmid16870886">{{cite journal | vauthors = Smith C, Rahman T, Toohey N, Mazurkiewicz J, Herrick-Davis K, Teitler M | title = Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor | journal = Molecular Pharmacology | volume = 70 | issue = 4 | pages = 1264–70 | date = October 2006 | pmid = 16870886 | doi = 10.1124/mol.106.024612 }}</ref><ref name="pmid18996971">{{cite journal | vauthors = Knight JA, Smith C, Toohey N, Klein MT, Teitler M | title = Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists | journal = Molecular Pharmacology | volume = 75 | issue = 2 | pages = 374–80 | date = February 2009 | pmid = 18996971 | pmc = 2671286 | doi = 10.1124/mol.108.052084 }}</ref>
{{Div col|colwidth=30em}}
* [[Bromocriptine]]<ref name="pmid18996971"/>
* [[Lisuride]]<ref name="pmid18996971"/>
* [[Metergoline]]<ref name="pmid18996971"/>
* [[Methiothepin]]<ref name="pmid16870886"/>
* [[Paliperidone]]<ref name="pmid16870886"/>
* [[Risperidone]]<ref name="pmid16870886"/>
{{Div col end}}
 
== See also ==
{{Div col|colwidth=30em}}
* [[5-HT receptor]]
* [[5-HT receptor]]
* [[5-HT1 receptor|5-HT<sub>1</sub> receptor]]
* [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]
* [[5-HT3 receptor|5-HT<sub>3</sub> receptor]]
* [[5-HT4 receptor|5-HT<sub>4</sub> receptor]]
* [[5-HT5 receptor|5-HT<sub>5</sub> receptor]]
* [[5-HT6 receptor|5-HT<sub>6</sub> receptor]]
{{Div col end}}


==References==
== References ==
{{reflist|2}}
{{Reflist|30em}}


==Further reading==
== External links ==
{{refbegin | 2}}
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2337 | title = 5-HT<sub>7</sub> | accessdate = | authorlink = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
{{PBB_Further_reading
* {{UCSC gene info|HTR7}}
| citations =
*{{cite journal  | author=Hoyer D, Hannon JP, Martin GR |title=Molecular, pharmacological and functional diversity of 5-HT receptors. |journal=Pharmacol. Biochem. Behav. |volume=71 |issue= 4 |pages= 533-54 |year= 2002 |pmid= 11888546 |doi=  }}
*{{cite journal  | author=Raymond JR, Mukhin YV, Gelasco A, ''et al.'' |title=Multiplicity of mechanisms of serotonin receptor signal transduction. |journal=Pharmacol. Ther. |volume=92 |issue= 2-3 |pages= 179-212 |year= 2002 |pmid= 11916537 |doi= }}
*{{cite journal  | author=Gelernter J, Rao PA, Pauls DL, ''et al.'' |title=Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. |journal=Genomics |volume=26 |issue= 2 |pages= 207-9 |year= 1995 |pmid= 7601444 |doi=  }}
*{{cite journal  | author=Ullmer C, Schmuck K, Kalkman HO, Lübbert H |title=Expression of serotonin receptor mRNAs in blood vessels. |journal=FEBS Lett. |volume=370 |issue= 3 |pages= 215-21 |year= 1995 |pmid= 7656980 |doi=  }}
*{{cite journal  | author=Bard JA, Zgombick J, Adham N, ''et al.'' |title=Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. |journal=J. Biol. Chem. |volume=268 |issue= 31 |pages= 23422-6 |year= 1993 |pmid= 8226867 |doi=  }}
*{{cite journal  | author=Lovenberg TW, Baron BM, de Lecea L, ''et al.'' |title=A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. |journal=Neuron |volume=11 |issue= 3 |pages= 449-58 |year= 1993 |pmid= 8398139 |doi=  }}
*{{cite journal  | author=Heidmann DE, Metcalf MA, Kohen R, Hamblin MW |title=Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization. |journal=J. Neurochem. |volume=68 |issue= 4 |pages= 1372-81 |year= 1997 |pmid= 9084407 |doi=  }}
*{{cite journal  | author=Erdmann J, Nöthen MM, Shimron-Abarbanell D, ''et al.'' |title=The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. |journal=Mol. Psychiatry |volume=1 |issue= 5 |pages= 392-7 |year= 1997 |pmid= 9154233 |doi=  }}
*{{cite journal  | author=Jasper JR, Kosaka A, To ZP, ''et al.'' |title=Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b). |journal=Br. J. Pharmacol. |volume=122 |issue= 1 |pages= 126-32 |year= 1997 |pmid= 9298538 |doi= 10.1038/sj.bjp.0701336 }}
*{{cite journal  | author=Lassig JP, Vachirasomtoon K, Hartzell K, ''et al.'' |title=Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder. |journal=Am. J. Med. Genet. |volume=88 |issue= 5 |pages= 472-5 |year= 1999 |pmid= 10490701 |doi=  }}
*{{cite journal  | author=Krobert KA, Levy FO |title=The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects. |journal=Br. J. Pharmacol. |volume=135 |issue= 6 |pages= 1563-71 |year= 2002 |pmid= 11906971 |doi= 10.1038/sj.bjp.0704588 }}
*{{cite journal | author=Norum JH, Hart K, Levy FO |title=Ras-dependent ERK activation by the human G(s)-coupled serotonin receptors 5-HT4(b) and 5-HT7(a). |journal=J. Biol. Chem. |volume=278 |issue= 5 |pages= 3098-104 |year= 2003 |pmid= 12446729 |doi= 10.1074/jbc.M206237200 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Slominski A, Pisarchik A, Zbytek B, ''et al.'' |title=Functional activity of serotoninergic and melatoninergic systems expressed in the skin. |journal=J. Cell. Physiol. |volume=196 |issue= 1 |pages= 144-53 |year= 2003 |pmid= 12767050 |doi= 10.1002/jcp.10287 }}
*{{cite journal  | author=Simonin F, Karcher P, Boeuf JJ, ''et al.'' |title=Identification of a novel family of G protein-coupled receptor associated sorting proteins. |journal=J. Neurochem. |volume=89 |issue= 3 |pages= 766-75 |year= 2004 |pmid= 15086532 |doi= 10.1111/j.1471-4159.2004.02411.x }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Brüss M, Kiel S, Bönisch H, ''et al.'' |title=Decreased agonist, but not antagonist, binding to the naturally occurring Thr92Lys variant of the h5-HT7(a) receptor. |journal=Neurochem. Int. |volume=47 |issue= 3 |pages= 196-203 |year= 2005 |pmid= 15896881 |doi= 10.1016/j.neuint.2005.03.003 }}
*{{cite journal  | author=Ikeda M, Iwata N, Kitajima T, ''et al.'' |title=Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population. |journal=Neuropsychopharmacology |volume=31 |issue= 4 |pages= 866-71 |year= 2006 |pmid= 16192982 |doi= 10.1038/sj.npp.1300901 }}
}}
{{refend}}


{{NLM content}}
{{NLM content}}
{{membrane-protein-stub}}
{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
[[Category:G protein coupled receptors]]
{{Serotonergics}}
 
{{DEFAULTSORT:5-Ht7 Receptor}}
[[Category:Serotonin receptors]]

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The 5-HT7 receptor is a member of the GPCR superfamily of cell surface receptors and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT)[1] The 5-HT7 receptor is coupled to Gs (stimulates the production of the intracellular signaling molecule cAMP)[2][3] and is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels.[3] This receptor has been a drug development target for the treatment of several clinical disorders.[4] The 5-HT7 receptor is encoded by the HTR7 gene, which in humans is transcribed into 3 different splice variants.[5]

Function

When the 5-HT7 receptor is activated by serotonin, it sets off a cascade of events starting with release of the stimulatory G protein Gs from the GPCR complex. Gs in turn activates adenylate cyclase which increases intracellular levels of the second messenger cAMP.

The 5-HT7 receptor plays a role in smooth muscle relaxation within the vasculature and in the gastrointestinal tract.[1] The highest 5-HT7 receptor densities are in the thalamus and hypothalamus, and it is present at higher densities also in the hippocampus and cortex. The 5-HT7 receptor is involved in thermoregulation, circadian rhythm, learning and memory, and sleep. It is also speculated that this receptor may be involved in mood regulation, suggesting that it may be a useful target in the treatment of depression.[6][7]

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.[5] The h5-HT7(a) is the full length receptor (445 amino acids),[3] 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.[5] Drug binding affinities are similar across the three human splice variants;[8] however, inverse agonist efficacies appear to differ between the splice variants.[9]

Discovery

In 1983, evidence for a 5-HT1-like receptor was first found.[10] Ten years later, 5-HT7 receptor was cloned and characterized.[3] It has since become clear that the receptor described in 1983 is 5-HT7.[11]

Clinical significance

This receptor gene is a candidate locus for involvement in autism and other neuropsychiatric conditions.[12]

Ligands

Numerous orthosteric ligands of moderate to high affinity are known. Signaling biased ligands were discovered and developed in 2018.[13]

Agonists

Agonists mimic the effects of the endogenous ligand, which is serotonin at the 5-HT7 receptor (↑cAMP).

Antagonists

Neutral antagonists (also known as silent antagonists) bind the receptor and have no intrinsic activity but will block the activity of agonists or inverse agonists. Inverse agonists inhibit the constitutive activity of the receptor, producing functional effects opposite to those of agonists (at the 5-HT7 receptor: ↓cAMP).[23][24] Neutral antagonists and inverse agonists are typically referred to collectively as "antagonists" and, in the case of the 5-HT7 receptor, differentiation between neutral antagonists and inverse agonists is problematic due to differing levels inverse agonist efficacy between receptor splice variants. For instance, mesulergine and metergoline are reported to be neutral antagonists at the h5-HT7(a) and h5-HT7(d) receptor isoforms but these drugs display marked inverse agonist effects at the h5-HT7(b) splice variant.[9]

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.[32] Inactivating antagonists all likely interact with the 5-HT7 receptor in an irreversible/pseudo-irreversible manner, as is the case with [3H]risperidone.[33][34]

See also

References

  1. ↑ 1.0 1.1 Vanhoenacker P, Haegeman G, Leysen JE (February 2000). "5-HT7 receptors: current knowledge and future prospects". Trends in Pharmacological Sciences. 21 (2): 70–7. doi:10.1016/S0165-6147(99)01432-7. PMID 10664612.
  2. ↑ Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC (September 1993). "Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation". Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8547–51. doi:10.1073/pnas.90.18.8547. PMC 47394. PMID 8397408.
  3. ↑ 3.0 3.1 3.2 3.3 Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL (November 1993). "Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase". The Journal of Biological Chemistry. 268 (31): 23422–6. PMID 8226867.
  4. ↑ Mnie-Filali O, Lambás-Señas L, Zimmer L, Haddjeri N (December 2007). "5-HT7 receptor antagonists as a new class of antidepressants". Drug News & Perspectives. 20 (10): 613–8. doi:10.1358/dnp.2007.20.10.1181354. PMID 18301795.
  5. ↑ 5.0 5.1 5.2 Heidmann DE, Metcalf MA, Kohen R, Hamblin MW (April 1997). "Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization". Journal of Neurochemistry. 68 (4): 1372–81. doi:10.1046/j.1471-4159.1997.68041372.x. PMID 9084407.
  6. ↑ Hedlund PB, Sutcliffe JG (September 2004). "Functional, molecular and pharmacological advances in 5-HT7 receptor research". Trends in Pharmacological Sciences. 25 (9): 481–6. doi:10.1016/j.tips.2004.07.002. PMID 15559250.
  7. ↑ Naumenko VS, Popova NK, Lacivita E, Leopoldo M, Ponimaskin EG (July 2014). "Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders". CNS Neuroscience & Therapeutics. 20 (7): 582–90. doi:10.1111/cns.12247. PMID 24935787.
  8. ↑ Krobert KA, Bach T, Syversveen T, Kvingedal AM, Levy FO (June 2001). "The cloned human 5-HT7 receptor splice variants: a comparative characterization of their pharmacology, function and distribution". Naunyn-Schmiedeberg's Archives of Pharmacology. 363 (6): 620–32. doi:10.1007/s002100000369. PMID 11414657.
  9. ↑ 9.0 9.1 Krobert KA, Levy FO (March 2002). "The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects". British Journal of Pharmacology. 135 (6): 1563–71. doi:10.1038/sj.bjp.0704588. PMC 1573253. PMID 11906971.
  10. ↑ Feniuk W, Humphrey PP, Watts AD (December 1983). "5-Hydroxytryptamine-induced relaxation of isolated mammalian smooth muscle". European Journal of Pharmacology. 96 (1–2): 71–8. doi:10.1016/0014-2999(83)90530-7. PMID 6662198.
  11. ↑ Hoyer D, Hannon JP, Martin GR (April 2002). "Molecular, pharmacological and functional diversity of 5-HT receptors". Pharmacology Biochemistry and Behavior. 71 (4): 533–54. doi:10.1016/S0091-3057(01)00746-8. PMID 11888546.
  12. ↑ Lassig JP, Vachirasomtoon K, Hartzell K, Leventhal M, Courchesne E, Courchesne R, Lord C, Leventhal BL, Cook EH (October 1999). "Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder". American Journal of Medical Genetics. 88 (5): 472–5. doi:10.1002/(SICI)1096-8628(19991015)88:5<472::AID-AJMG7>3.0.CO;2-G. PMID 10490701.
  13. ↑ Kim Y, Kim H, Lee J, Lee JK, Min SJ, Seong J, Rhim H, Tae J, Lee HJ, Choo H (August 2018). "Discovery of β-Arrestin Biased Ligands of 5-HT7R". J. Med. Chem. 61 (16): 7218–7233. doi:10.1021/acs.jmedchem.8b00642. PMID 30028132.
  14. ↑ Sprouse J, Reynolds L, Li X, Braselton J, Schmidt A (January 2004). "8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock through increases in cAMP production". Neuropharmacology. 46 (1): 52–62. doi:10.1016/j.neuropharm.2003.08.007. PMID 14654097.
  15. ↑ 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
  16. ↑ Brenchat A, Ejarque M, Zamanillo D, Vela JM, Romero L (August 2011). "Potentiation of morphine analgesia by adjuvant activation of 5-HT7 receptors". Journal of Pharmacological Sciences. 116 (4): 388–91. doi:10.1254/jphs.11039sc. PMID 21778664.
  17. ↑ Brenchat A, Nadal X, Romero L, Ovalle S, Muro A, Sánchez-Arroyos R, Portillo-Salido E, Pujol M, Montero A, Codony X, Burgueño J, Zamanillo D, Hamon M, Maldonado R, Vela JM (June 2010). "Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity". Pain. 149 (3): 483–94. doi:10.1016/j.pain.2010.03.007. PMID 20399562.
  18. ↑ Brenchat A, Romero L, García M, Pujol M, Burgueño J, Torrens A, Hamon M, Baeyens JM, Buschmann H, Zamanillo D, Vela JM (February 2009). "5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice". Pain. 141 (3): 239–47. doi:10.1016/j.pain.2008.11.009. PMID 19118950.
  19. ↑ Powell SL, Gödecke T, Nikolic D, Chen SN, Ahn S, Dietz B, Farnsworth NR, van Breemen RB, Lankin DC, Pauli GF, Bolton JL (December 2008). "In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent". Journal of Agricultural and Food Chemistry. 56 (24): 11718–26. doi:10.1021/jf803298z. PMC 3684073. PMID 19049296.
  20. ↑ Leopoldo M, Lacivita E, Contino M, Colabufo NA, Berardi F, Perrone R (August 2007). "Structure-activity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides, a class of 5-HT7 receptor agents. 2". Journal of Medicinal Chemistry. 50 (17): 4214–21. doi:10.1021/jm070487n. PMID 17649988.
  21. ↑ Leopoldo M, Berardi F, Colabufo NA, Contino M, Lacivita E, Niso M, Perrone R, Tortorella V (December 2004). "Structure-affinity relationship study on N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides, a new class of 5-hydroxytryptamine7 receptor agents". Journal of Medicinal Chemistry. 47 (26): 6616–24. doi:10.1021/jm049702f. PMID 15588097.
  22. ↑ Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, Latacz G, Handzlik J, Kieć-Kononowicz K, Wierońska JM, Woźniak M, Cieślik P, Bugno R, Staroń J, Bojarski AJ (May 2017). "Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol". Scientific Reports. 7 (1444): 1444. doi:10.1038/s41598-017-00822-4. PMC 5431432. PMID 28473721.
  23. ↑ Pittalà V, Salerno L, Modica M, Siracusa MA, Romeo G (September 2007). "5-HT7 receptor ligands: recent developments and potential therapeutic applications". Mini Reviews in Medicinal Chemistry. 7 (9): 945–60. doi:10.2174/138955707781662663. PMID 17897083.
  24. ↑ Leopoldo M (March 2004). "Serotonin(7) receptors (5-HT(7)Rs) and their ligands". Current Medicinal Chemistry. 11 (5): 629–61. doi:10.2174/0929867043455828. PMID 15032609.
  25. ↑ Volk B, Barkóczy J, Hegedus E, Udvari S, Gacsályi I, Mezei T, Pallagi K, Kompagne H, Lévay G, Egyed A, Hársing LG, Spedding M, Simig G (April 2008). "(Phenylpiperazinyl-butyl)oxindoles as selective 5-HT7 receptor antagonists". Journal of Medicinal Chemistry. 51 (8): 2522–32. doi:10.1021/jm070279v. PMID 18361484.
  26. ↑ Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL (July 2009). "Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo". Psychopharmacology. 205 (1): 119–28. doi:10.1007/s00213-009-1521-8. PMC 2821721. PMID 19337725.
  27. ↑ 27.0 27.1 Romero G, Pujol M, Pauwels PJ (October 2006). "Reanalysis of constitutively active rat and human 5-HT7(a) receptors in HEK-293F cells demonstrates lack of silent properties for reported neutral antagonists". Naunyn-Schmiedeberg's Archives of Pharmacology. 374 (1): 31–9. doi:10.1007/s00210-006-0093-y. PMID 16967291.
  28. ↑ Forbes IT, Dabbs S, Duckworth DM, Jennings AJ, King FD, Lovell PJ, Brown AM, Collin L, Hagan JJ, Middlemiss DN, Riley GJ, Thomas DR, Upton N (February 1998). "(R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl) propyl]benzenesulfonamide: the first selective 5-HT7 receptor antagonist". Journal of Medicinal Chemistry. 41 (5): 655–7. doi:10.1021/jm970519e. PMID 9513592.
  29. ↑ 29.0 29.1 Mahé C, Loetscher E, Feuerbach D, Müller W, Seiler MP, Schoeffter P (July 2004). "Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors". European Journal of Pharmacology. 495 (2–3): 97–102. doi:10.1016/j.ejphar.2004.05.033. PMID 15249157.
  30. ↑ Lovell PJ, Bromidge SM, Dabbs S, Duckworth DM, Forbes IT, Jennings AJ, King FD, Middlemiss DN, Rahman SK, Saunders DV, Collin LL, Hagan JJ, Riley GJ, Thomas DR (February 2000). "A novel, potent, and selective 5-HT(7) antagonist: (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl) phen ol (SB-269970)". Journal of Medicinal Chemistry. 43 (3): 342–5. doi:10.1021/jm991151j. PMID 10669560.
  31. ↑ Forbes IT, Douglas S, Gribble AD, Ife RJ, Lightfoot AP, Garner AE, Riley GJ, Jeffrey P, Stevens AJ, Stean TO, Thomas DR (November 2002). "SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties". Bioorganic & Medicinal Chemistry Letters. 12 (22): 3341–4. doi:10.1016/S0960-894X(02)00690-X. PMID 12392747.
  32. ↑ Zhang J, Ferguson SS, Barak LS, Aber MJ, Giros B, Lefkowitz RJ, Caron MG (1997). "Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization". Receptors & Channels. 5 (3–4): 193–9. PMID 9606723.
  33. ↑ 33.0 33.1 33.2 33.3 Smith C, Rahman T, Toohey N, Mazurkiewicz J, Herrick-Davis K, Teitler M (October 2006). "Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor". Molecular Pharmacology. 70 (4): 1264–70. doi:10.1124/mol.106.024612. PMID 16870886.
  34. ↑ 34.0 34.1 34.2 34.3 Knight JA, Smith C, Toohey N, Klein MT, Teitler M (February 2009). "Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists". Molecular Pharmacology. 75 (2): 374–80. doi:10.1124/mol.108.052084. PMC 2671286. 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.

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