Molecular biology of serotonin (5-HT) receptors

The recent cloning of three types of 5-hydroxytryptamine (5-HT, serotonin) receptors substantiates radioligand-based definitions of 5-HT receptors, and provides a framework in which to understand the function and evolution of the receptors. The primary sequences determined by molecular cloning of the 5-HT1c, 5-HT1a and 5-HT2 receptors place each of these 5-HT receptor subtypes into the class of G protein-coupled receptors. These receptors all share similar functional and structural features. Each receptor is positioned in the lipid bilayer with seven membrane-spanning domains and corresponding intracellular and extracellular domains. By analogy to the known functional structures of the beta-adrenergic receptor, the binding site of 5-HT is proposed to be in the membrane domains and the intracellular domain is important for G protein interaction. The primary sequences and the second messenger systems of the receptors indicate the 5-HT2 and 5-HT1c receptors are closely related, whereas the 5-HT1a receptor is more distantly related to the 5-HT2 and 5-HT1c receptors.