EXPRESSION CLONING OF THE DOPAMINE DI RECEPTOR

DOPAMINERGIC NEUROTRANSMISSION PLAYS A SIGNIFICANT ROLE IN PSYCHIATRIC AND EXTRAPYRAMIDAL DISORDERS, ENDOCRINE FUNCTION, AND VASODILATION. TO BETTER UNDERSTAND THE DOPAMINE D1 RECEPTOR AS A POTENTIAL SITE FOR DRUG DEVELOPMENT, IT IS PLANNED TO IDENTIFY AND CHARACTERIZE THE RECEPTOR GENE BY EXPRESSION CDNA CLONING. IN PHASE I OF THIS PROJECT, A RADIOLABELED LIGAND-BINDING ASSAY TO SCREEN INTACT CELLS TRANSFECTED WITH A CDNA LIBRARY WILL BE DEVELOPED. THIS ASSAY WILL PROVIDE A GENERAL SCREENING METHOD TO ISOLATE ANY SINGLE SUBUNIT NEUROTRANSMITTER RECEPTOR GENE BY CDNA EXPRESSION. IN PHASE II, THE ASSAY WILL BE USED TO OBTAIN THE DOPAMINE D1 RECEPTOR. SEQUENCE ANALYSIS OF THE GENE WILL DETERMINE ITS STRUCTURE AND RELATION TO OTHER MEMBERS OF THE G PROTEIN-COUPLED RECEPTOR SUPERFAMILY. HETEROLOGOUS EXPRESSION OF THE D1 RECEPTOR WILL PERMIT STUDY OF ITS PHARMACOLOGY IN ISOLATION AND ACCELERATED DEVELOPMENT OF HIGHLY SPECIFIC DRUGS FOR THIS SITE. THESE D1-SELECTIVE AGENTS MAY BE OF THERAPEUTIC VALUE IN THE TREATMENT OF PSYCHOTIC DISORDERS, HYPERTENSION, AND CONGESTIVE HEART FAILURE.