Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.
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.
Grailhe
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R
Center for Neurobiology and Behavior, Columbia University, 722 West 168 Street, New York, NY 10032, USA. rgrailhe@pasteur.fr
Grabtree
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GW
Hen
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D019556:COS Cells; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D019143:Evolution, Molecular; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; D004247:DNA