A HUMAN SEROTONIN 1D RECEPTOR VARIANT (5HT1D-BETA) ENCODED BY AN INTRONLESS GENE ON CHROMOSOME-6

An intronless gene encoding a serotonin receptor (5HT1D-beta) has been cloned and functionally expressed in mammalian fibroblast cultures. Based on the deduced amino acid sequence, the gene encodes a 390-amino acid protein displaying considerable homology, within putative transmembrane domains (almost-equal-to 75% identity) to the canine and human 5HT1D receptors. Membranes prepared from CHO cells stably expressing the receptor bound [H-3]serotonin with high affinity (K(d) 4 nM) and displayed a pharmacological profile consistent, but not identical, with that of the characterized serotonin 5HTlD receptor. Most notably, metergoline and serotonergic piperazine derivatives, as a group, display 3- to 8-fold lower affinity for the 5HT1D-beta receptor than for the 5HT1D receptor, whereas both receptors display similar affinities for tryptamine derivatives, including the antimigraine drug sumatriptan. Northern blot analysis revealed an mRNA of almost-equal-to 5.5 kilobases expressed in human and monkey frontal cortex, medulla, striatum, hippocampus and amygdala but not in cerebellum, olfactory tubercle, and pituitary. The 5HT1D-beta gene maps to human chromosome 6. The existence of multiple neuronal 5HT1D-like receptors may help account for some of the complexities associated with [H-3]serotonin binding patterns in native membranes.