Abstract: 5-HT receptors consist of at least three distinct types of molecular structures: G protein-coupled receptors, ligand-gated ion channels, and transporters. The group of G protein-coupled 5-HT receptors contains the greatest number of known 5-HT receptor subtypes. The evolutionary relationships between the known G protein-coupled 5-HT receptor subtypes were determined by a phylogenetic tree analysis. The primordial G protein-coupled 5-HT receptor differentiated into three clearly discernible receptor subclasses as indicated by the three major branches within the phylogenetic, tree: 5-HT1 receptors (which include 5-HT5 and 5-HT7 receptors), 5-HT2 receptors, and 5-HT6 receptors. The differentiation of the primordial 5-HT receptor into the three major receptor subclasses occurred approximately 750 million years ago. The 5-HT1 receptor family or branch includes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F receptors and certain 5-HT receptors identified in invertebrates such as the 5-HTdro2A, 5-HTdro2B and 5-HTsnail receptors (Saudou et al., 1992; Sugamori et al., 1993). The invertebrate 5-HT receptors and the mammalian 5-HT1 receptors share the ability to inhibit adenylyl cyclase. The 5-HT7 receptors are positively coupled to adenylyl cyclase (Shen et al., 1993; Plassat et al., 1993). The 5-HT5 receptors (Plassat et al., 1992; Erlander et al., 1993; Matthes et al., 1993) are equally homologous to the 5-HT1 and 5-HT7 receptors (approximately 32% homologous). The second messenger system of 5-HT5 receptors remains to be identified (Plassat et al., 1992; Matthes et al., 1993). The 5-HT2 family or branch of G protein-coupled 5-HT receptors includes 5-HT2A, 5-HT2B (formerly called 5-HT2F receptors) and 5-HT2C (formerly called 5-HT1C receptors). These receptors are positively coupled to phosphatidyl inositol turn-over. The 5-HT6 receptor is positively linked to adenylyl cyclase, thus making it functionally similar to 5-HT7 receptors. 5-HT3 receptors directly activate a 5-HT-gated cation channel which rapidly and transiently depolarizes a variety of neurons. The third major molecular recognition system for 5-HT are the transporter proteins. Transporters consist of 12 membrane spanning proteins and represent a large gene family encoding Na+ and Cl− dependent transport proteins. Given the age of the 5-HT receptor system, it can be predicted that other subtypes remain to be identified. Classification of 5-HT receptors by means of a molecular evolutionary approach will allow for immediate classification after sequencing with pharmacological and transductional data in the years ahead.
Publication Year: 1997
Publication Date: 1997-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 2
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