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 cyclase. 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.

A primordial dopamine D1‐like adenylyl cyclase‐linked receptor from Drosophila melanogaster displaying poor affinity for benzazepines

“…The single letter amino acid code is used. Sequences sources are as follows: human DI [31,53,54], monkey D1 [55], rat D1A [53], opposum D1A [56], goldfish D1 [57], Xen D1A, D1B and D1C [6], human D5 [29,58,59], rat D1B [60], chicken D1A, D1B, DID [7]. receptors; and 49% to human D5 and chicken DIB receptors.…”

Interactions of the Novel Antipsychotic Aripiprazole (OPC-14597) with Dopamine and Serotonin Receptor Subtypes

“…Received April 17, 1998; revised August 27, 1998; accepted September 21, 1998. (Zhou et al 1990;Monsma et al 1990;Sunahara et al 1990;Dearry et al 1990) and D 1B (Tiberi et al 1991) or D 5 (Sunahara et al 1991], both of these linked functionally to stimulation of cAMP synthesis, and preferentially recognizing 1-phenyl-tetrahydrobenzazepines (e.g., SCH23390). The D 2 -like receptors come from at least three genes and include multiple splice variants.…”

Reduction in Acetylcholine Release in the Hippocampus of Dopamine D5 Receptor-Deficient Mice

“…The D 1 -like receptor subfamily includes the molecularly defined d1 and d5 subtypes (Dearry et al, 1990;Sunahara et al, 1990Sunahara et al, , 1991Zhou et al, 1990), which are both expressed in the hippocampus (Bergson et al, 1995;Tiberi et al, 1991). These two subtypes share approximately 50% sequence homology (80% in the transmembrane domains), which translates into a highly similar pharmacological profile (Seeman and Van Tol, 1993;Sunahara et al, 1991;Tiberi et al, 1991).…”