Classification and signaling characteristics of 5-HT receptors: toward the concept of 5-HT receptosomes

Abstract Serotonin (5-hydroxytryptamine, 5-HT) is one of the extracellular messengers capable of activating the largest number of receptors (17 receptors belonging to seven classes—5-HT1-7—defined first on a pharmacological basis and then on their gene sequence). Alternative splicing and RNA editing add to this diversity. Most 5-HT receptors belong to the G protein–coupled receptor (GPCR) family except for 5-HT3 receptors that are ionic channels. Their activation gives rise to a huge complexity of intracellular signaling events that depend or not on G protein activation and underlie the diversity of physiological functions of 5-HT. Assembly of 5-HT receptors into heteromers with distinct 5-HT receptors or other GPCRs, as well as their physical association with protein partners further increase the versatility of serotonergic signaling and the complexity of its regulation. These interactions also offer novel opportunities for therapeutic interventions in disorders related to dysfunctions of serotonergic systems.