Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.

Article Details

Citation

Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW

Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.

J Neurochem. 1996 Jan;66(1):47-56.

PubMed ID
8522988 [ View in PubMed
]
Abstract

We describe the cloning and characterization of a human 5-HT6 serotonin receptor. The open reading frame is interrupted by two introns in positions corresponding to the third cytoplasmic loop and the third extracellular loop. The human 5-HT6 cDNA encodes a 440-amino-acid polypeptide 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 human 5-HT6 amino acid sequence is 89% similar to the corrected rat sequence. The recombinant human 5-HT6 receptor is positively coupled to adenylyl cyclase and has pharmacological properties similar to the rat receptor with high affinity for several typical and atypical antipsychotics, including clozapine. The receptor is expressed in several human brain regions, most prominently in the caudate nucleus. The gene for the receptor maps to the human chromosome region 1p35-p36. This localization overlaps that established for the serotonin 5-HT1D alpha receptor, suggesting that these may be closely linked. Comparison of genomic and cDNA clones for the human 5-HT6 receptor also reveals an Rsal restriction fragment length polymorphism within the coding region.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
5-hydroxytryptamine receptor 6P50406Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Amitriptyline5-hydroxytryptamine receptor 6Ki (nM)65N/AN/ADetails
Amoxapine5-hydroxytryptamine receptor 6Ki (nM)50N/AN/ADetails
Chlorpromazine5-hydroxytryptamine receptor 6Ki (nM)19N/AN/ADetails
Clozapine5-hydroxytryptamine receptor 6Ki (nM)9.5N/AN/ADetails
Dimethyltryptamine5-hydroxytryptamine receptor 6Ki (nM)68N/AN/ADetails
Loxapine5-hydroxytryptamine receptor 6Ki (nM)27N/AN/ADetails
Mianserin5-hydroxytryptamine receptor 6Ki (nM)55N/AN/ADetails
Olanzapine5-hydroxytryptamine receptor 6Ki (nM)10N/AN/ADetails
Quetiapine5-hydroxytryptamine receptor 6Ki (nM)33N/AN/ADetails