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5-ht5a receptor

Family: 5-Hydroxytryptamine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 357 7q36.1 HTR5A 5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled 16
Mouse 7 357 5 A3-B Htr5a 5-hydroxytryptamine (serotonin) receptor 5A 12
Rat 7 357 4q11 Htr5a 5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled 4
Previous and Unofficial Names
Names References
5-HT5α 4
REC17 4
5-HT5A 16
5HT5-
5-HT5A
5-hydroxytryptamine (serotonin) receptor 5A
5-HT-5A
5HT5A
MR22
5-hydroxytryptamine receptor 5A
serotonin receptor 5A
Htr5
Database Links
ChEMBL Target 10624 (Hs), 10625 (Mm), 10626 (Rn)
Ensembl ENSG00000157219 (Hs), ENSMUSG00000039106 (Mm), ENSRNOG00000007066 (Rn)
Entrez Gene 3361 (Hs), 15563 (Mm), 25689 (Rn)
GeneCards HTR5A (Hs)
GenitoUrinary Development Molecular Anatomy Project Htr5a (Mm)
HomoloGene 22461 (Hs)
Human Protein Reference Database 03198 (Hs)
InterPro P47898 (Hs), P30966 (Mm), P35364 (Rn)
KEGG Gene hsa:3361 (Hs), mmu:15563 (Mm), rno:25689 (Rn)
OMIM 601305 (Hs)
PharmGKB Gene PA29558 (Hs)
Protein Ontology (PRO) PRO:000001169 (Hs)
RefSeq Nucleotide NM_024012 (Hs), NM_008314 (Mm), NM_013148 (Rn)
RefSeq Protein NP_076917 (Hs), NP_032340 (Mm), NP_037280 (Rn)
TreeFam ENSG00000157219 (Hs), ENSMUSG00000039106 (Mm), ENSRNOG00000007066 (Rn)
UniGene Hs. 65791 (Hs)
UniProt P47898 (Hs), P30966 (Mm), P35364 (Rn)
Wikipedia 5-ht5a receptor
5-Hydroxytryptamine receptors
Search for 3D structures on the PDB
Search by keyword: 5-Hydroxytryptamine receptors 5-ht5a receptor Search by accession number: P35364, P47898, P30966
Natural/Endogenous Ligand(s)
5-HT
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]LSD Hs Full agonist 9.7 pKd 7
[3H]5-CT Hs Full agonist 8.6 pKd 7
5-CT Rn Full agonist 7.9 pKi 4
5-CT Hs Full agonist 7.6 – 7.7 pKi 7,16
5-CT Mm Full agonist 7.3 – 7.8 pKi 7,12,19
5-HT Hs Full agonist 6.7 – 6.9 pKi 7,16
5-HT Rn Full agonist 6.6 pKi 4
RU 24969 Mm Full agonist 6.5 pKi 12
5-HT Mm Full agonist 6.0 – 6.6 pKi 7,12,19
donitriptan Hs Full agonist 6.1 pKi 10
RU 24969 Hs Full agonist 6.0 pKi 16
8-OH-DPAT Mm Full agonist 5.9 pKi 7,12
(+)-lysergic acid Mm Full agonist 5.7 pKi 19
8-OH-DPAT Hs Full agonist 5.6 – 5.7 pKi 7,16
TFMPP Mm Full agonist 5.6 pKi 12
EMDT Hs Full agonist 5.3 pKi 6
sumatriptan Hs Full agonist 5.3 pKi 7,16
sumatriptan Mm Full agonist 4.8 pKi 7,12
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
methiothepin Hs Antagonist 8.5 – 8.9 pKi 7,16
ergotamine Hs Antagonist 8.0 – 8.7 pKi 7,16
ergotamine Rn Antagonist 8.2 pKi 4
SB 699551 Hs Antagonist 8.2 pKi 2
ergotamine Mm Antagonist 7.4 – 8.4 pKi 7,12,19
ritanserin Hs Antagonist 7.6 pKi 7
methiothepin Rn Antagonist 7.5 pKi 4
ritanserin Mm Antagonist 7.4 pKi 7
methiothepin Mm Antagonist 7.0 pKi 7,12
methysergide Hs Antagonist 7.0 pKi 16
methysergide Mm Antagonist 6.3 – 7.2 pKi 12,19
methysergide Rn Antagonist 6.7 pKi 4
clozapine Hs Antagonist 6.0 – 6.5 pKi 7,16
metergoline Hs Antagonist 6.2 pKi 16
bufotenine Mm Antagonist 5.3 – 6.0 pKi 12,19
yohimbine Mm Antagonist 4.9 – 6.0 pKi 12,19
clozapine Mm Antagonist 5.3 pKi 7
MPDT Hs Antagonist 5.3 pKi 6
yohimbine Hs Antagonist 5.3 pKi 16
(-)-propranolol Hs Antagonist 5.1 pKi 16
ketanserin Hs Antagonist 4.7 pKi 16
View species-specific antagonist tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  A pertussis toxin-sensitive inhibition of ADP-ribosyl cyclase has been observed [14].
References:  5,9
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  Coupling to the GIRK1 channel has been observed [7].
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 [13]).
References:  14
Tissue Distribution
Resting lymphocytes (see comments).
Species:  Human
Technique:  RT-PCR.
References:  11
Brain: amygdala, caudate nucleus, cerebellum, hypothalamus, substantia nigra, thalamus.
Expression not seen in any peripheral tissues.
Species:  Human
Technique:  RT-PCR.
References:  16
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:  15
Brain: Medial habenula > olfactory bulb, caudate putamen, neocortex, hippocampus.
Species:  Mouse
Technique:  Radioligand binding.
References:  8
Brain: piriform cortex, hippocampus, amygdala, septum, thalamic nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  4
Brain: carotid body, superior cervical ganglion and petrosal ganglion.
Species:  Rat
Technique:  Immunocytochemistry and RT-PCR.
References:  18
Spinal cord: dorsal horn, dorsolateral nucleus, lamina X.
Species:  Rat
Technique:  immunocytochemistry.
References:  3
Brain: hippocampus, hypothalamus > cortex, thalamus, pons, striatum, medulla.
Species:  Rat
Technique:  Northern blotting.
References:  4
Expression Datasets

Click here to show/hide data

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]

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Functional Assays
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:  5,9
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:  1,14
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:  14
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:  14
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:  14
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:  7
Physiological Functions
Modulation of exploratory behavior.
Species:  Mouse
Tissue:  In vivo.
References:  8
Regulation of suprachiasmatic nuclei neuronal firing (potential role in the control of circadian rhythms).
Species:  Rat
Tissue:  Hypothalamic slices.
References:  17
Physiological Consequences of Altering Gene Expression
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:  8
Phenotypes, Alleles and Disease Models Mouse data from MGI

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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

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1. Carson, M. J., Thomas, E. A., Danielson, P. E. and Sutcliffe, J. G. (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: 317-326. [PMID:8856328]

2. Corbett, D. F., Heightman, T. D., Moss, S. F., Bromidge, S. M., Coggon, S. A., Longley, M. J., Roa, A. M., Williams, J. A. and Thomas, D. R. (2005) Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry. Bioorg Med Chem Lett, 15: 4014-4018. [PMID:16002289]

3. Doly, S., Fischer, J., Brisorgueil, M. J., Verge, D. and 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: 316-329. [PMID:15282708]

4. Erlander, M. G., Lovenberg, T. W., Baron, B. M., De Lecea, L., Danielson, P. E., Racke, M., Slone, A. L., Siegel, B. W., Foye, P. E., 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: 3452-3456. [PMID:7682702]

5. Francken, B. J., Jurzak, M., Vanhauwe, J. F., Luyten, W. H. and Leysen, J. E. (1998) The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells. Eur J Pharmacol, 361: 299-309. [PMID:9865521]

6. Glennon, R. A., Lee, M., Rangisetty, J. B., Dukat, M., Roth, B. L., Savage, J. E., McBride, A., Rauser, L., Hufeisen, S. and Lee, D. K. (2000) 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem, 43: 1011-1018. [PMID:10715164]

7. Grailhe, R., Grabtree, G. W. and 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: 157-167. [PMID:11343685]

8. Grailhe, R., Waeber, C., Dulawa, S. C., Hornung, J. P., Zhuang, X., Brunner, D., Geyer, M. A. and Hen, R. (1999) Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor. Neuron, 22: 581-591. [PMID:10197537]

9. Hurley, P. T., McMahon, R. A., Fanning, P., O'Boyle, K. M., Rogers, M. and Martin, F. (1998) Functional coupling of a recombinant human 5-HT5A receptor to G-proteins in HEK-293 cells. Br J Pharmacol, 124: 1238-1244. [PMID:9720796]

10. John, G. W., Pauwels, P. J., Perez, M., Halazy, S., Le Grand, B., Verscheure, Y., Valentin, J. P., Palmier, C., Wurch, T., Chopin, P., Marien, M., Kleven, M. S., Koek, W., Assie, M. B., Carilla-Durand, E., Tarayre, J. P. and Colpaert, F. C. (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: 83-95. [PMID:10381763]

11. Marazziti, D., Ori, M., Nardini, M., Rossi, A., Nardi, I. and Cassano, G. B. (2001) mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes. Neuropsychobiology, 43: 123-126. [PMID:11287788]

12. Matthes, H., Boschert, U., Amlaiky, N., Grailhe, R., Plassat, J. L., Muscatelli, F., Mattei, M. G. and Hen, R. (1993) Mouse 5-hydroxytryptamine 5A and 5-hydroxytryptamine 5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol. Pharmacol., 43: 313-319. [PMID:8450829]

13. Noda, M., Higashida, H., Aoki, S. and Wada, K. (2004) Multiple signal transduction pathways mediated by 5-HT receptors. Mol Neurobiol, 29: 31-39. [PMID:15034221]

14. Noda, M., Yasuda, S., Okada, M., Higashida, H., Shimada, A., Iwata, N., Ozaki, N., Nishikawa, K., Shirasawa, S., Uchida, M., Aoki, S. and Wada, K. (2003) Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways. J Neurochem, 84: 222-232. [PMID:12558985]

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

16. Rees, S., den Daas, I., Foord, S., Goodson, S., Bull, D., Kilpatrick, G. and Lee, M. (1994) Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett., 355: 242-246. [PMID:7988681]

17. Sprouse, J., Reynolds, L., Braselton, J. and Schmidt, A. (2004) Serotonin-induced phase advances of SCN neuronal firing in vitro: a possible role for 5-HT5A receptors?. Synapse, 54: 111-118. [PMID:15352136]

18. Wang, Z. Y., Keith, I. M., Beckman, M. J., Brownfield, M. S., Vidruk, E. H. and Bisgard, G. E. (2000) 5-HT5a receptors in the carotid body chemoreception pathway of rat. Neurosci Lett, 278: 9-12. [PMID:10643788]

19. Weiss, H. M., Haase, W., Michel, H. and Reilander, H. (1995) Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization. FEBS Lett, 377: 451-456. [PMID:8549774]

To cite this database page, please use the following:

Rodrigo Andrade, Nicholas M. Barnes, Gordon Baxter, Joel Bockaert, Theresa Branchek, Marlene L. Cohen, Aline Dumuis, Richard M. Eglen, Manfred Göthert, Mark Hamblin, Michel Hamon, Paul R. Hartig, René Hen, Katharine Herrick-Davis, Rebecca Hills, Daniel Hoyer, Patrick P. A. Humphrey, Klaus Peter Latté, Luc Maroteaux, Graeme R. Martin, Derek N. Middlemiss, Ewan Mylecharane, Stephen J. Peroutka, Pramod R. Saxena, Andrew Sleight, Carlos M. Villalon, Frank Yocca.
5-Hydroxytryptamine receptors: 5-ht5a receptor. Last modified on 10/02/2012. Accessed on 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=10.


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