Top ▲

5-HT5A receptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 10

Nomenclature: 5-HT5A receptor

Family: 5-Hydroxytryptamine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 357 7q36.2 HTR5A 5-hydroxytryptamine receptor 5A 17
Mouse 7 357 5 13.24 cM Htr5a 5-hydroxytryptamine (serotonin) receptor 5A 13
Rat 7 357 4q11 Htr5a 5-hydroxytryptamine receptor 5A 5
Previous and Unofficial Names Click here for help
5-HT [5] | 5HT5- | 5-HT-5A | MR22 | serotonin receptor 5A | Htr5 | 5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled
Database Links Click here for help
Specialist databases
GPCRDB 5ht5a_human (Hs), 5ht5a_mouse (Mm), 5ht5a_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
5-hydroxytryptamine

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]LSD Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.7 pKd 8
pKd 9.7 (Kd 2x10-10 M) [8]
[3H]5-CT Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.6 pKd 8
pKd 8.6 (Kd 2.5x10-9 M) [8]
5-CT Small molecule or natural product Click here for species-specific activity table Rn Full agonist 7.9 pKi 5
pKi 7.9 [5]
5-CT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.6 – 7.7 pKi 8,17
pKi 7.6 – 7.7 [8,17]
5-CT Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.3 – 7.8 pKi 8,13,20
pKi 7.3 – 7.8 [8,13,20]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 6.7 – 6.9 pKi 8,17
pKi 6.7 – 6.9 [8,17]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.6 pKi 5
pKi 6.6 [5]
RU 24969 Small molecule or natural product Click here for species-specific activity table Mm Full agonist 6.5 pKi 13
pKi 6.5 [13]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 6.0 – 6.6 pKi 8,13,20
pKi 6.0 – 6.6 [8,13,20]
donitriptan Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.1 pKi 11
pKi 6.1 [11]
RU 24969 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pKi 17
pKi 6.0 [17]
8-OH-DPAT Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.9 pKi 8,13
pKi 5.9 [8,13]
lysergic acid Small molecule or natural product Mm Full agonist 5.7 pKi 20
pKi 5.7 [20]
8-OH-DPAT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.6 – 5.7 pKi 8,17
pKi 5.6 – 5.7 [8,17]
TFMPP Small molecule or natural product Click here for species-specific activity table Mm Full agonist 5.6 pKi 13
pKi 5.6 [13]
EMDT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.3 pKi 7
pKi 5.3 [7]
sumatriptan Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.3 pKi 8,17
pKi 5.3 [8,17]
sumatriptan Small molecule or natural product Approved drug Mm Full agonist 4.8 pKi 8,13
pKi 4.8 [8,13]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
methiothepin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 – 8.9 pKi 8,17
pKi 8.5 – 8.9 [8,17]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 – 8.7 pKi 8,17
pKi 8.0 – 8.7 [8,17]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.2 pKi 5
pKi 8.2 [5]
SB 699551 Small molecule or natural product Hs Antagonist 8.2 pKi 3
pKi 8.2 (Ki 6.3x10-9 M) [3]
ergotamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 7.4 – 8.4 pKi 8,13,20
pKi 7.4 – 8.4 [8,13,20]
ritanserin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.6 pKi 8
pKi 7.6 [8]
methiothepin Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.5 pKi 5
pKi 7.5 [5]
ritanserin Small molecule or natural product Ligand has a PDB structure Mm Antagonist 7.4 pKi 8
pKi 7.4 [8]
methiothepin Small molecule or natural product Click here for species-specific activity table Mm Antagonist 7.0 pKi 8,13
pKi 7.0 [8,13]
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 pKi 17
pKi 7.0 [17]
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 6.3 – 7.2 pKi 13,20
pKi 6.3 – 7.2 [13,20]
methysergide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 6.7 pKi 5
pKi 6.7 [5]
vortioxetine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.7 pKi 1
pKi 6.7 (Ki 2.2x10-7 M) [1]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.0 – 6.5 pKi 8,17
pKi 6.0 – 6.5 [8,17]
metergoline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 17
pKi 6.2 [17]
bufotenine Small molecule or natural product Click here for species-specific activity table Mm Antagonist 5.3 – 6.0 pKi 13,20
pKi 5.3 – 6.0 [13,20]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 4.9 – 6.0 pKi 13,20
pKi 4.9 – 6.0 [13,20]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 5.3 pKi 8
pKi 5.3 [8]
MPDT Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.3 pKi 7
pKi 5.3 [7]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.3 pKi 17
pKi 5.3 [17]
(-)-propranolol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.1 pKi 17
pKi 5.1 [17]
ketanserin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 4.7 pKi 17
pKi 4.7 [17]
View species-specific antagonist tables
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  A pertussis toxin-sensitive inhibition of ADP-ribosyl cyclase has been observed [15].
References:  6,10
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  Coupling to the GIRK1 channel has been observed [8].
It should be noted that as well as reports showing that the receptor couples to many different signalling pathways, there are also reports showing that the receptor has difficulty coupling to any intracellular pathways (for a review see [14]).
References:  15
Tissue Distribution Click here for help
Resting lymphocytes (see comments).
Species:  Human
Technique:  RT-PCR.
References:  12
Brain: amygdala, caudate nucleus, cerebellum, hypothalamus, substantia nigra, thalamus.
Expression not seen in any peripheral tissues.
Species:  Human
Technique:  RT-PCR.
References:  17
Brain: neocortical regions (mainly layers II-III and V-VI), hippocampus (dentate gyrus and pyramidal cell layer of CA1 and CA3 fields), cerebellum (Purkinje cells, dentate nucleus and granule cells).
Species:  Human
Technique:  in situ hybridisation.
References:  16
Brain: Medial habenula > olfactory bulb, caudate putamen, neocortex, hippocampus.
Species:  Mouse
Technique:  Radioligand binding.
References:  9
Brain: piriform cortex, hippocampus, amygdala, septum, thalamic nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  5
Brain: carotid body, superior cervical ganglion and petrosal ganglion.
Species:  Rat
Technique:  Immunocytochemistry and RT-PCR.
References:  19
Spinal cord: dorsal horn, dorsolateral nucleus, lamina X.
Species:  Rat
Technique:  immunocytochemistry.
References:  4
Brain: hippocampus, hypothalamus > cortex, thalamus, pons, striatum, medulla.
Species:  Rat
Technique:  Northern blotting.
References:  5
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Measurement of cAMP levels in HEK 293 cells transfected with the human 5-ht5a receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibiton of cAMP accumulation.
References:  6,10
Measurement of cAMP levels in gioma cells transfected with the rat 5-ht5a receptor.
Species:  Rat
Tissue:  Glioma cells.
Response measured:  Inhibition of cAMP accumulation.
References:  2,15
Measurement of outward currents in C6 glioma cells transfected with the human 5-ht2a receptor.
Species:  Human
Tissue:  Glioma cells.
Response measured:  Stimulation of a Ca2+-sensitive K+ outward current.
References:  15
Measurement of ADP-ribosyl cyclase activity in C6 glioma cells transfected with the human 5-ht5a receptor.
Species:  Human
Tissue:  Glioma cells.
Response measured:  Inhibition of ADP ribosyl cyclase.
References:  15
Measurement of IP3 levels in C6 glioma cells transfected with the human 5-ht5a receptor.
Species:  Human
Tissue:  Glioma cells.
Response measured:  Increase in IP3 levels.
References:  15
Measurement of K+ channel activity in Xenopus oocytes transfected with the 5-ht5a receptor and GIRK1 channels.
Species:  Human
Tissue:  Xenopus oocytes.
Response measured:  GIRK1 activation.
References:  8
Physiological Functions Click here for help
Modulation of exploratory behavior.
Species:  Mouse
Tissue:  In vivo.
References:  9
Regulation of suprachiasmatic nuclei neuronal firing (potential role in the control of circadian rhythms).
Species:  Rat
Tissue:  Hypothalamic slices.
References:  18
Physiological Consequences of Altering Gene Expression Click here for help
5-ht5a receptor knockout mice exhibit increased exploratory behavior in response to novel environments or LSD.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Htr5atm1Rhn Htr5atm1Rhn/Htr5atm1Rhn
involves: 129S2/SvPas
MGI:96283  MP:0003107 abnormal response to novelty PMID: 10197537 
Htr5atm1Rhn Htr5atm1Rhn/Htr5atm1Rhn
involves: 129S2/SvPas
MGI:96283  MP:0001415 increased exploration in new environment PMID: 10197537 
Htr5atm1Dgen Htr5atm1Dgen/Htr5atm1Dgen
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:96283  MP:0002169 no abnormal phenotype detected
General Comments
The human 5-ht5b receptor, found on chromosome 2q14.1, has high structural homology to the 5-HT5A receptor subtype. It is not a functional GPCR due to interruption by a stop codon in the coding region of the human gene. However, this stop codon is not found in the rodent gene and so the rodent 5-ht5b receptor may be functional.

References

Show »

1. Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A et al.. (2011) Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J. Med. Chem., 54 (9): 3206-21. [PMID:21486038]

2. Carson MJ, Thomas EA, Danielson PE, Sutcliffe JG. (1996) The 5HT5A serotonin receptor is expressed predominantly by astrocytes in which it inhibits cAMP accumulation: a mechanism for neuronal suppression of reactive astrocytes. Glia, 17 (4): 317-26. [PMID:8856328]

3. Corbett DF, Heightman TD, Moss SF, Bromidge SM, Coggon SA, Longley MJ, Roa AM, Williams JA, Thomas DR. (2005) Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry. Bioorg. Med. Chem. Lett., 15 (18): 4014-8. [PMID:16002289]

4. Doly S, Fischer J, Brisorgueil MJ, Vergé D, Conrath M. (2004) 5-HT5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature. J. Comp. Neurol., 476 (4): 316-29. [PMID:15282708]

5. Erlander MG, Lovenberg TW, Baron BM, de Lecea L, Danielson PE, Racke M, Slone AL, Siegel BW, Foye PE, Cannon K et al.. (1993) Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain. Proc. Natl. Acad. Sci. U.S.A., 90 (8): 3452-6. [PMID:7682702]

6. Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE. (1998) The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells. Eur. J. Pharmacol., 361 (2-3): 299-309. [PMID:9865521]

7. Glennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK. (2000) 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J. Med. Chem., 43 (5): 1011-8. [PMID:10715164]

8. Grailhe R, Grabtree GW, Hen R. (2001) Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution. Eur. J. Pharmacol., 418 (3): 157-67. [PMID:11343685]

9. Grailhe R, Waeber C, Dulawa SC, Hornung JP, Zhuang X, Brunner D, Geyer MA, Hen R. (1999) Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor. Neuron, 22 (3): 581-91. [PMID:10197537]

10. Hurley PT, McMahon RA, Fanning P, O'Boyle KM, Rogers M, Martin F. (1998) Functional coupling of a recombinant human 5-HT5A receptor to G-proteins in HEK-293 cells. Br. J. Pharmacol., 124 (6): 1238-44. [PMID:9720796]

11. John GW, Pauwels PJ, Perez M, Halazy S, Le Grand B, Verscheure Y, Valentin JP, Palmier C, Wurch T, Chopin P et al.. (1999) F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine. J. Pharmacol. Exp. Ther., 290 (1): 83-95. [PMID:10381763]

12. Marazziti D, Ori M, Nardini M, Rossi A, Nardi I, Cassano GB. (2001) mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes. Neuropsychobiology, 43 (3): 123-6. [PMID:11287788]

13. Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R. (1993) Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol. Pharmacol., 43 (3): 313-9. [PMID:8450829]

14. Noda M, Higashida H, Aoki S, Wada K. (2004) Multiple signal transduction pathways mediated by 5-HT receptors. Mol. Neurobiol., 29 (1): 31-9. [PMID:15034221]

15. Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, Ozaki N, Nishikawa K, Shirasawa S, Uchida M et al.. (2003) Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways. J. Neurochem., 84 (2): 222-32. [PMID:12558985]

16. Pasqualetti M, Ori M, Nardi I, Castagna M, Cassano GB, Marazziti D. (1998) Distribution of the 5-HT5A serotonin receptor mRNA in the human brain. Brain Res. Mol. Brain Res., 56 (1-2): 1-8. [PMID:9602024]

17. Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M. (1994) Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett., 355 (3): 242-6. [PMID:7988681]

18. Sprouse J, Reynolds L, Braselton J, Schmidt A. (2004) Serotonin-induced phase advances of SCN neuronal firing in vitro: a possible role for 5-HT5A receptors?. Synapse, 54 (2): 111-8. [PMID:15352136]

19. Wang ZY, Keith IM, Beckman MJ, Brownfield MS, Vidruk EH, Bisgard GE. (2000) 5-HT5a receptors in the carotid body chemoreception pathway of rat. Neurosci. Lett., 278 (1-2): 9-12. [PMID:10643788]

20. Weiss HM, Haase W, Michel H, Reiländer H. (1995) Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization. FEBS Lett., 377 (3): 451-6. [PMID:8549774]

Contributors

Show »

How to cite this page