MULTIPLE SEROTONIN RECEPTOR SUBTYPES - MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION

The field of serotonin (5HT) receptor pharmacology has been at least a s dramatically altered by the advent of molecular neurobiology and rec ombinant DNA techniques as has any other neurotransmitter receptor fie ld. The principal reason for this is the unforeseen multitude of genes expressing different types of 5HT receptors. Classic pharmacological studies as well as radioligand binding studies convinced workers in th e field that there were multiple 5HT receptors. The extent of that mul tiplicity was not generally foreseen. At the time of this writing, no less than 13 5HT receptor genes have been cloned and functionally expr essed. In addition, a fourteenth receptor has been well studied and wi ll undoubtedly be cloned in the near future. These novel 5HT receptor clones are appearing at an astonishing rate. All 13 receptors have bee n cloned between the years 1987 to 1993, with more than half of the cl ones appearing in the literature in the last 18 months. Furthermore, t here is no indication that all of the 5HT receptors present in the mam malian genome have been cloned. In fact, there are classic pharmacolog ical data as well as radioligand binding data that implicate the exist ence of additional 5HT receptor subtypes not yet fully defined or clon ed. Bringing order to this rapid outpouring of information at this tim e is a very difficult task. Not only is there a great multiplicity of receptor subtypes, each with a unique pharmacology and distribution, b ut there are species variants of 5HT receptors. In order to provide a concise and timely review, this article focuses on the strategies used to clone and express multiple 5HT receptors. Unique properties of the various receptors are emphasized.