CLONING, CHARACTERIZATION, AND CHROMOSOMAL LOCALIZATION OF A HUMAN 5-HT6 SEROTONIN RECEPTOR

We describe the cloning and characterization of a human 5-HT6 serotoni n receptor. The open reading frame is interrupted by two introns in po sitions corresponding to the third cytoplasmic loop and the third extr acellular loop. The human 5-HT6 cDNA encodes a 440-amino-acid polypept ide whose sequence diverges significantly from that published for the rat 5-HT6 receptor. Resequencing of the rat cDNA revealed a sequencing error producing a frame shift within the open reading frame. The huma n 5-HT6 amino acid sequence is 89% similar to the corrected rat sequen ce. The recombinant human 5-HT6 receptor is positively coupled to aden ylyl cyclase and has pharmacological properties similar to the rat rec eptor with high affinity for several typical and atypical antipsychoti cs, including clozapine. The receptor is expressed in several human br ain regions, most prominently in the caudate nucleus. The gene for the receptor maps to the human chromosome region 1p35-p36. This localizat ion overlaps that established for the serotonin 5-HT1D alpha receptor, suggesting that these may be closely linked. Comparison of genomic an d cDNA clones for the human 5-HT6 receptor also reveals an Rsal restri ction fragment length polymorphism within the coding region.