5-HT1E receptor

Function

The function of the 5-HT1E receptor is unknown due to the lack of selective pharmacological tools, specific antibodies, and permissive animal models. The 5-HT1E receptor gene lacks polymorphisms amongst humans (few mutations), indicating a high degree of evolutionary conservation of genetic sequence, which suggests that the 5-HT1E receptor has an important physiological role in humans. It is hypothesized that the 5-HT1E receptor is involved in the regulation of memory in humans due to the high abundance of receptors in the frontal cortex, hippocampus, and olfactory bulb, all of which are regions of the brain integral to memory regulation.

This receptor is unique among the serotonin receptors in that it is not known to be expressed by rats or mouse species, all of which lack the gene encoding the 5-HT1E receptor. However the genomes of the pig, rhesus monkey, and several lagomorphs (including rabbit) as well as the guinea pig each encode a homologous 5-HT1E receptor gene. The guinea pig is the most likely candidate for future study of 5-HT1E receptor function in vivo. The expression of 5-HT1E receptors in the guinea pig brain has been pharmacologically confirmed; 5-HT1E receptor expression patterns of the human and guinea pig brains appear to be similar. In the human cortex, the expression of 5-HT1E undergoes a marked transition during adolescence, in a way that is strongly correlated with the expression of 5-HT1B.

The most closely related receptor to the 5-HT1E is the 5-HT1F receptor. They share 57% amino acid sequence homology and have some pharmacological characteristics in common. Both receptors are Gi-coupled (inhibit adenylate cyclase activity) and both receptors have high affinities for 5-HT and low affinities for 5-carboxyamidotryptaine and mesulergine. However, due to major differences in brain expression patterns, these receptors are unlikely to mediate similar functions in humans. For example, 5-HT1E receptors are abundant in the hippocampus but are not detectable in the striatum (caudate and putamen of the human brain), while the opposite is true for the 5-HT1F receptor. Thus, conclusions about the function of the 5-HT1E receptor cannot be ascribed to the function of the 5-HT1F receptor, and vice versa.

Selective ligands

No highly selective 5-HT1E ligands are available yet. [3H]5-HT remains the only radioligand available with high affinity for the 5-HT1E receptor (5nM).

Agonists

• BRL-54443 (5-Hydroxy-3-(1-methylpiperidin-4-yl)-1H-indole) - mixed 5-HT1E/1F agonist

Antagonists

None as yet.

References

References

1. (Aug 1989). "Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein". Journal of Neurochemistry.
2. (Jun 1992). "Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype". Proceedings of the National Academy of Sciences of the United States of America.
3. (Aug 1994). "Assignment of the gene encoding the 5-HT1E serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15". Genomics.
4. "Entrez Gene: HTR1E 5-hydroxytryptamine (serotonin) receptor 1E".
5. (Apr 2009). "Guinea pig hippocampal 5-HT(1E) receptors: a tool for selective drug development". Journal of Neurochemistry.
6. (Apr 1995). "Lack of genetically determined structural variants of the human serotonin-1E (5-HT1E) receptor protein points to its evolutionary conservation". Brain Research. Molecular Brain Research.
7. (Jan 2004). "Molecular cloning and pharmacological characterization of the guinea pig 5-HT1E receptor". European Journal of Pharmacology.
8. (Jul 2014). "Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence". European Neuropsychopharmacology.
9. (Aug 1999). "A review of central 5-HT receptors and their function". Neuropharmacology.
10. (Jan 1993). "Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase". Proceedings of the National Academy of Sciences of the United States of America.