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 (( 3 H)5-CT; K D =2.8 nM) and iodinated lysergic acid diethylamide (( 125 I)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.
European Journal of Pharmacology – Elsevier
Published: Apr 27, 2001
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