Molecular cloning and expression of the gene for a human D₁ dopamine receptor

Abstract

THE diverse physiological actions of dopamine are mediated by its interaction with two basic types of G protein-coupled receptor, D₁ and D₂, which stimulate and inhibit, respectively, the enzyme adenylyl cyclase¹. Alterations in the number or activity of these receptors may be a contributory factor in diseases such as Parkinson's disease and schizophrenia. Here we describe the isolation and characterization of the gene encoding a human D₁ dopamine receptor. The coding region of this gene is intronless, unlike the gene encoding the D₂ dopamine receptor. The D₁ receptor gene encodes a protein of 446 amino acids having a predicted relative molecular mass of 49,300 and a transmembrane topology similar to that of other G protein-coupled receptors. Transient or stable expression of the cloned gene in host cells established specific ligand binding and functional activity characteristic of a D₁ dopamine receptor coupled to stimulation of adenylyl cyclase. Northern blot analysis and in situ hybridization revealed that the messenger RNA for this receptor is most abundant in caudate, nucleus accumbens and olfactory tubercle, with little or no mRNA detectable in substantia nigra, liver, kidney, or heart. Several observations from this work in conjunction with results from other studies are consistent with the idea that other D₁ dopamine receptor subtypes may exist.