Human 5-HT5 receptors: the 5-HT5A receptor is functional but the 5-HT5B receptor was lost during mammalian evolution
Abstract
We have isolated from a human genomic library the human 5-hydroxytryptamine 5-HT(5A) and 5-HT(5B) genes. The human 5-HT(5A) gene encodes a protein with similar characteristics to its mouse homologue. When expressed in monkey COS-7 cells, the human 5-HT(5A) receptor displayed a high affinity for tritiated 5-carbamidotryptamine ([3H]5-CT; K(D)=2.8 nM) and iodinated lysergic acid diethylamide ([125I]LSD; K(D)=187 pM). These binding sites displayed the following displacement profile: Ergotamine>Methiothepin>5-CT, Ritanserin>5-HT. Reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed the presence of human 5-HT(5A) mRNA in the central nervous system but not in peripheral organs. When expressed in Xenopus oocytes, the 5-HT(5A) receptor was able to couple to the inwardly rectifying K(+) channel, GIRK(1). In contrast to the human 5-HT(5A) gene and the mouse 5-HT(5B) gene, the human 5-HT(5B) gene does not encode a functional protein because its coding sequence is interrupted by stop codons. Our results suggest, therefore, that the 5-HT(5B) receptor has been lost during evolution after the divergence between rodents and primates. The 5-HT(5B) receptor is the first example of a brain-specific protein that is absent in human.
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Htr5b was found in ependymal cells and a subset of 5-HT neurons.
“Htr5b, which is a pseudogene in humans (Grailhe et al., 2001), was found in ependymal cells and a subset of 5-HT neurons.”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Grailhe et al., 2001
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- Authors
- Grailhe, R., Grabtree, G. W., & Hen, R.
- Affiliations
- Columbia University (US)
- Corresponding author
- Grailhe, Régis
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 418
- Issue
- 3
- Pages
- 157-167
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2041052694
- Cited by
- 130
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 5
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute of Technology
- National Institutes of Health (5r01da009862-08)
- National Institute on Drug Abuse (DA09862)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- 5-HT5A receptor, serotonin receptors, receptor evolution, lysergic acid diethylamide, inwardly rectifying potassium channels, GIRK1, brain-specific proteins
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding, Competitive, Cell Line, DNA, Genes, Humans, Membranes, Molecular Sequence Data, Phylogeny, Radioligand Assay, Receptors, Serotonin, Gene Expression, Sequence Alignment, 3T3 Cells, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Evolution, Molecular, COS Cells, Mice
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