5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates.

In the last few years, molecular biology has led to the cloning and characterization of several 5-HT receptors (serotonin receptors) in vertebrates and in invertebrates. These studies have allowed identification not only of 5-HT receptors already described but also of novel subtypes. The molecular cloning of 13 different mammalian receptor subtypes revealed an unexpected heterogeneity among 5-HT receptors. Except for the 5-HT3 receptors which are ligand-gated ion channel receptors, all the other 5-HT receptors belong to the large family of receptors interacting with G proteins. Based on their amino acid sequence homology and coupling to second messengers these receptors can be divided into distinct families: the 5-HT1 family contains receptors that are negatively coupled to adenylate cyclase: the 5-HT2 family includes receptors that stimulate phospholipase C; the adenylyl cyclase stimulatory receptors are a heterogeneous group including the 5-HT4 receptor which has not yet been cloned, the Drosophila 5-HTdro1 receptor and two mammalian receptors tentatively named 5-HT6 and 5-HT7 receptors. The 5-HT5A and 5-HT5B receptors might constitute a new family of 5-HT receptors whose effectors are unknown. This review focusses on the molecular characteristics of the cloned 5-HT receptors such as their structure, their effector systems and their distribution within the central nervous system. The existence of a large number of receptors with distinct signalling properties and expression patterns might enable a single substance like 5-HT to generate simultaneously a large panel of effects in many brain structures. The availability of the genes encoding these receptors has already allowed a partial characterization of their structure-function relationship and will probably allow in the future a dissection of the contribution of each of these receptor subtypes to physiology and behaviour.