DISTINCT 5-HT(1B) AND 5-HT(1D) SEROTONIN RECEPTORS IN RAT - STRUCTURAL AND PHARMACOLOGICAL COMPARISON OF THE 2 CLONED RECEPTORS

We and others have recently cloned the genes encoding the human 5-HT1D (5-HT1Dα) and 5-HT1B (5-HT1Dβ) serotonin receptors. Because of the history of profound species differences in the pharmacology of these receptor subtypes, we also cloned the homologous genes for these two receptors in rat. The rat 5-HT1D receptor gene, like that of the rat 5-HT1B receptor, is intronless, encoding a 374-amino acid polypeptide 90% identical to its human homologue. The rat 5-HT1D and rat 5-HT1B receptors are 61% identical in their deduced amino acid sequences. The availability of both the rat 5-HT1B and 5-HT1D genes allowed direct comparison of the pharmacological properties of the two receptors expressed in transfected cells as assessed using 5-[3H]HT binding assays. Unlike the rat 5-HT1B receptor, which is pharmacologically dimorphic with respect to its human homologue, the rat 5-HT1D receptor has an almost identical profile compared to the human 5-HT1D receptor. (±)-Cyanopindolol and (-)-propranolol are more than 100-fold selective for the rat 5-HT1B receptor over the rat 5-HT1D receptor, while mianserin is more than 100-fold selective for the rat 5-HT1D receptor. The rat 5-HT1D receptor is expressed in cells of the dorsal raphe and thus may serve as an additional type of serotonin autoreceptor. This constitutes the first unambiguous characterization of a 5-HT1D receptor in rat and demonstrates its relationship to the 5-HT1B receptor in rat as well as to the 5-HT1D and 5-HT1B receptors in human. © 1992.