CLONING OF THE SEROTONIN 5-HT1B AND 5-HT1D RECEPTORS

THE 5-HT1B AND 5-HT1D RECEPTORS APPEAR TO PLAY A SIGNIFICANTROLE IN AT LEAST FOUR MEDICALLY IMPORTANT PROCESSES: THERMOREGULATION, APPETITE CONTROL, ANXIETY, AND OBSESSIVE-COMPULSIVE DISORDERS. THESE RECEPTORS ARE DIFFICULT TO STUDY DUE TO THEIR LOW DENSITY, INTERFERENCE BY OTHER SEROTONIN-RECEPTOR SITES, AND LARGE SPECIES DIFFERENCES IN THEIR DISTRIBUTION. FURTHERMORE, FEW USEFUL DRUGS ARE CURRENTLY AVAILABLE FOR STUDYING THE BIOLOGY OF THESE RECEPTORS. IN AN EFFORT TO BETTER UNDERSTAND THESE POTENTIAL SITES FOR DRUG DEVELOPMENT, IT IS PLANNED TO CLONE AND CHARACTERIZE THE 5-HT1B AND 5-HT1D RECEPTORS FROM CDNA AND GENOMIC LIBRARIES. THE 5-HT1B AND 5-HT1D RECEPTOR CLONES WILL SERVE AS PROBES FOR DETERMINING TISSUE LEVELS OF GENE EXPRESSION AS WELL AS THE GENOMIC STRUCTURE OF THE RECEPTOR GENES. SEQUENCE ANALYSIS OF THESE CLONES WILL BE USEFUL IN DETERMINING THEIRRELATIONS TO EACH OTHER, TO OTHER SEROTONIN-RECEPTOR SUBTYPES, AND TO OTHER MEMBERS OF THE G-PROTEIN-RECEPTOR SUPERFAMILY. HETEROLOGOUS EXPRESSION OF THESE RECEPTORS IN MAMMALIAN CELLLINES SHOULD ALSO HELP IN FURTHER DELINEATING THEIR PHARMACOLOGICAL PROPERTIES AND SECOND-MESSENGER COUPLING, PROVIDING LEADS FOR THE DEVELOPMENT OF NEW THERAPEUTIC AGENTS FOR APPETITE CONTROL, ANXIETY, AND OBSESSIVE-COMPULSIVE DISORDERS.