5-HT6 receptor

5-hydroxytryptamine (serotonin) receptor 6
Identifiers
Symbols HTR6; 5-HT6; 5-HT6R
External IDs OMIM: 601109 MGI: 1196627 HomoloGene: 673 IUPHAR: 5-HT6 GeneCards: HTR6 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3362 15565
Ensembl ENSG00000158748 ENSMUSG00000028747
UniProt P50406 Q14AW8
RefSeq (mRNA) NM_000871 NM_021358.2
RefSeq (protein) NP_000862 NP_067333.1
Location (UCSC) Chr 1:
19.99 – 20.01 Mb		 Chr 4:
138.62 – 138.63 Mb
PubMed search [1] [2]

The 5-HT6 receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).[1] It is a G protein-coupled receptor (GPCR) that is coupled to Gs/Go and mediates excitatory neurotransmission.[1] HTR6 denotes the human gene encoding for the receptor.[2]

Contents

Distribution

The 5-HT6 receptor is expressed almost exclusively in the brain.[3] It is distributed in various areas including, but not limited to, the olfactory tubercle, cerebral cortex (frontal and entorhinal regions), nucleus accumbens, striatum, caudate nucleus, hippocampus, and the molecular layer of the cerebellum.[1][4][5] Based on its abundance in extrapyramidal, limbic, and cortical regions it can be suggested that the 5-HT6 receptor plays a role in functions like motor control, emotionality, cognition, and memory.[3][5][6]

Function

Blockade of central 5-HT6 receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas,[7][8][9][10] whereas activation enhances GABAergic signaling in a widespread manner.[11] Antagonism of 5-HT6 receptors also facilitates dopamine and norepinephrine release in the frontal cortex,[10][12] while stimulation has the opposite effect.[11]

Despite the 5-HT6 receptor having a functionally excitatory action, it is largely co-localized with GABAergic neurons and therefore produces an overall inhibition of brain activity.[11] In parallel with this, 5-HT6 antagonists improve cognition, learning, and memory,[13] and agents such as latrepirdine, Lu AE58054, and SB-742,457 are being developed as novel treatments for Alzheimer's disease and other dementias.[10][14][15] 5-HT6 antagonists have also been shown to reduce appetite and produce weight loss, and as a result, PRX-07034, BVT-5,182, and BVT-74,316 are being investigated for the treatment of obesity.[16][17]

Recently, the 5-HT6 agonists WAY-181,187 and WAY-208,466 have been demonstrated to be active in rodent models of depression, anxiety, and obsessive-compulsive disorder (OCD), and such agents may be useful treatments for these conditions.[11][18] Additionally, it can be inferred that 5-HT6 activation likely plays a major role in the therapeutic benefits of serotonergic antidepressants like the selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).

Ligands

A large number of selective 5-HT6 ligands have now been developed and this is a productive current area of research.[19][20][21][22][23][24][25]

Full agonists

Partial Agonists

Antagonists

Genetics

The receptor is encoded by the HTR6 gene. As the protein is a neuroreceptor it is possible that genetic variations in the gene would have an effect on brain, and research studies have investigated whether polymorphisms is associated with brain-related variables, such as neuropsychiatric disorders. For example, in 2004 one Chinese study reported an association between the C267T (rs1805054) polymorphism and Alzheimer's disease.[36] Others have studied the polymorphism in relation to Parkinson's disease.[37]

See also

References

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  2. ^ "Entrez Gene: HTR6 5-hydroxytryptamine (serotonin) receptor 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3362. 
  3. ^ a b Woolley ML, Marsden CA, Fone KC (February 2004). "5-ht6 receptors". Current Drug Targets. CNS and Neurological Disorders 3 (1): 59–79. doi:10.2174/1568007043482561. PMID 14965245. 
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  7. ^ Dawson LA, Nguyen HQ, Li P (May 2000). "In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate". British Journal of Pharmacology 130 (1): 23–6. doi:10.1038/sj.bjp.0703288. PMC 1572041. PMID 10780993. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1572041. 
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Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Signaling pathways
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By location
Other concepts
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)