Classification and Signaling Characteristics of 5-HT Receptors

Abstract Serotonin (5-hydroxytryptamine; 5-HT), along with its receptors, is one of the oldest molecular devices assuming intercellular communication, being present as soon as simple nervous systems appeared during evolution. 5-HT receptors (7 classes, 5-HT 1 to 5-HT 7 , coded by 17 different genes) are G protein-coupled receptors (GPCR) except for 5-HT 3 receptors, which are ionic channels. Splicing and editing add to the diversity of 5-HT receptors. They were first defined on a pharmacological basis and then on a gene structural basis, but the concordance between these two classifications is remarkable. The complexity of signaling events, including G protein-independent signaling of the GPCR classes, is not yet fully understood, and underscores the physiological importance of 5-HT. 5-HT receptors are associated with a large number of proteins involved in their localization, traffic and the fine-tuning signaling. Homodimerization and heterodimerization of 5-HT receptors with other GPCRs but also ligand-directed signaling (signaling dependent on the ligand and not only on the receptor) add to the complexity. Finally, 5-HT receptors are the targets of many therapeutic drugs on the market, in development and yet to be developed.