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, we proposed to identify and characterize the receptor gene by expression cDNA cloning. In Phase 1 of this project, we will develop a radiolabeled ligand binding assay to screen intact cells transfected with a cDNA library. This assay will provide us with a general screening method to isolate any single subunit neurotransmitter receptor gene by cDNA expression. In Phase II, we will utilize the assay 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 accelerate development of highly specific drugs for this site. These D1-selective agents may be of therapeutic value in treatment of psychotic disorders, hypertension, and congestive heart failure.
