Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.

Abstract

We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothepin > 5-carboxamidotryptamine > 5-HT. For REC17, the rank of potency was ergotamine > 5-carboxamidotryptamine > methiothepin > methysergide > 5-HT. Both were insensitive to 5-HT1A, 5-HTTD or 5-HT2 serotonergic ligands [8-hydroxy-2-(di-n-propylamino)tetralin, sumatriptan, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The mRNAs encoding MR22 were detected in the CAl region ofhippocampus, the medial habenula, and raphe nuclei. In contrast, mRNAs encoding REC17 were found throughout the rat central nervous system. We propose that REC17 and MR22, designated as 5-HT5. and 5-HTsp, represent a distinct subfamily of 5-HT receptors.Serotonin (5-hydroxytryptamine, 5-HT) regulates a wide variety of sensory, motor, and behavioral functions in the mammalian central nervous system. This biogenic amine neurotransmitter is synthesized by neurons in the raphe nuclei of the brainstem that project throughout the central nervous system, with the highest density in basal ganglia and limbic structures (1). Serotonergic transmission is thought to be involved with a variety of behaviors and psychiatric disorders including anxiety, sleep regulation, aggression, feeding, and depression (2, 3). Understanding how 5-HT mediates its diverse physiological actions requires the identification and isolation of the pertinent 5-HT receptors.

Functional characterization of the 5‐HT terminal autoreceptor in the guinea‐pig brain cortex

“…However, ketanserin is not an (Amlaiky et al, 1992;Adham et al, 1993;Lovenberg et al, 1993b), 5-HT5 (Erlander et al, 1993;Matthes et al, 1993), 5-HT6 (Monsma et al, 1993) and 5-HT7 (Lovenberg et al, 1993a;To et al, 1995). mRNA for the 5-HTIF, 5-HT5B and 5-HT7 receptors have been detected in the raphe nuclei (Bruinvels et al, 1994;Wisden et al, 1993;Erlander et al, 1993;To et al, 1995), suggesting that they have autoreceptor function. In the guinea-pig whole cortex the slopes of the agonist curves for 5-HT and 5-CT were shallow, which may also indicate the existence of multiple autoreceptors.…”

Central Serotonin2C Receptor: From Physiology to Pathology

“…Although the functional significance remains to be revealed, the interest in these receptor subtypes have increased after the demonstration that several antipsychotic drugs including clozapine, chloropramazine, risperidone and olanzapine display a significant affinity for these sites [24]. Two subtypes of the 5-HT 5 receptor (5-HT 5A and 5-HT 5B ), sharing 70% overall sequence identity, have been found in rodents, whereas only the 5-HT 5A subtype has been found in humans [25,26]. Recent studies have shown that the human recombinant 5-HT 5A receptor activation produced an inhibition of cAMP production, indicating negative coupling to cAMP via Gi and Go [27]; however, the receptor may also couple positively to cAMP.…”

The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

“…5-CT has nanomolar affinity for 5-HT 7 receptors [33,85], it also binds to 5-HT 1A , 5-HT 1B and 5-HT 1D receptors although with lower affinities [32,72,171]. In addition, 5-CT also expresses affinity for 5-HT 5 receptors [57] whereas it is less potent at 5-HT 4 receptors [38]. Boess and Martin [33] have reported that the affinity of 5-CT for 5-HT 4 receptors is approximatively 200-fold lower than for 5-HT 7 receptors.…”